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Background: Inflammation has a key role in the pathogenesis of psoriasis. Circulating cell-free DNA (CFD) is a marker of tissue cell damage closely associated with inflammation., Objectives: We aimed to understand the relation of CFD levels with psoriasis severity, defined by the Psoriasis Area and Severity Index (PASI), with inflammation and with psoriasis therapy., Methods: Forty-six patients with psoriasis vulgaris were evaluated before (T0) and after 12 weeks (T12) of treatment with narrowband ultraviolet light B (NB-UVB; n = 17), psoralen plus UVA (PUVA; n = 20) or topical therapy (n = 9). We evaluated interleukin (IL)-6 and circulating CFD levels., Results: Compared with controls, at T0, patients presented significantly higher levels of circulating CFD. CFD presented a significant positive correlation with IL-6 and a trend towards a positive correlation with PASI. Multiple linear regression analysis identified IL-6 as an independent variable associated with CFD circulating levels. As shown by the PASI score, a trend towards higher values of CFD was observed in the severe psoriasis forms; moderate and severe psoriasis presented also significantly higher CFD values, compared with control. Both NB-UVB and PUVA treatments significantly decreased the levels of CFD., Conclusions: Patients with psoriasis, at the active stage of the disease, presented an increased inflammation associated with raised circulating CFD levels, which seem to be linked to psoriasis severity. Both NB-UVB and PUVA, anti-inflammatory therapies, were effective in decreasing CFD values. We propose that the evaluation of circulating CFD may provide a new biomarker to monitor psoriasis, its severity and its treatment., (© 2013 British Association of Dermatologists.)

Background: Cardiovascular risk factors are found with significantly high frequency in psoriatic patients. Periods of remission and reactivation of lesions are common in psoriasis., Objective: Considering the association of chronic inflammation with the atherogenic process, we aimed to search for a possible relationship between the lipid profile, adipokine levels and body mass index (BMI) at the end of a successful treatment for psoriasis, and the length of remission of psoriasis., Methods: Forty-three patients were clinically and analytically studied after a successful treatment [as shown by Psoriasis Area and Severity Index (PASI)]--nine treated with topical agents, 17 with narrow-band UV light B (NB-UVB) and 17 with psoralen plus UVA-and were followed to record the length of remission., Results: The length of psoriasis remission correlated negatively and significantly with cholesterol levels, which correlated significantly and positively with C-reactive protein (CRP). In multiple linear regression analysis, cholesterol, CRP, PASI and BMI were associated with the length of remission. Patients with cholesterol levels <200 mg/dL (n = 13) presented a significantly longer remission, lower BMI and triglycerides values, and a trend towards lower PASI and CRP values than those with high cholesterol (n = 30). Considering patients according to the treatment used, cholesterol was also associated with length of remission, especially for patients treated with NB-UVB and topical therapy., Conclusion: Psoriasis patients with the highest cholesterol levels presented higher BMIs, triglycerides levels and shorter remission periods. Our data suggest that the identification of potentially treatable conditions, such as dyslipidaemia and obesity, and their adequate treatment may benefit psoriasis patients by increasing the length of remission of the disease.

Acitretin is currently used alone or combined with PUVA (psoralen + UVA) or with narrow-band ultraviolet B (NBUVB), to treat moderate and severe psoriasis. However, little is known about the potential genotoxic/carcinogenic risk and the cytostatic/cytotoxic effects of these treatments. Our aim was to study the cytotoxic and genotoxic effects of acitretin - alone or in combination with PUVA or NBUVB - by performing studies with blood from patients with psoriasis vulgaris who were treated with acitretin, acitretin+PUVA or acitretin+NBUVB for 12 weeks, and in vitro studies with blood from healthy volunteers, which was incubated with acitretin at different concentrations. The cytotoxic and genotoxic effects were evaluated by the cytokinesis-blocked micronucleus test and the comet assay. Our results show that psoriatic patients treated with acitretin alone or with acitretin+NBUVB, did not show genotoxic effects. In addition, these therapies reduced the rate of proliferation and induced apoptosis and necrosis of lymphocytes; the same occurred with lymphocyte cultures incubated with acitretin (1.2-20μM). The acitretin+PUVA reduced also the proliferation rate, and increased the necrotic lymphocytes. Our studies suggest that therapy with acitretin alone or combined with NBUVB, as used in psoriatic patients, does not show genotoxic effects, reduces the rate of proliferation and induces apoptosis and necrosis of lymphocytes. The combination of acitretin with PUVA also reduces the proliferation rate and increases the number of necrotic lymphocytes. However, as it induced slight genotoxic effects, further studies are needed to clarify its genotoxic potential., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Isotretinoin is a retinoic acid frequently used in monotherapy or combined with narrow-band ultraviolet B (NBUVB) irradiation to treat patients with acne and psoriasis vulgaris. As both diseases need frequent and/or prolonged therapeutic interventions, the study of the genotoxicity of retinoids becomes important. Our aim was to study the genotoxic effects of isotretinoin alone or combined with NBUVB. In vitro studies were performed in the absence of S9 metabolic activation using blood from five healthy volunteers, incubated 72 h with isotretinoin (1.2-20 μM) (i.e., at concentrations usually achieved in blood with therapeutic doses as well as at higher concentrations). In vivo studies were also performed using blood from two patients with acne and three patients with psoriasis vulgaris treated with isotretinoin in monotherapy (8 or 20mg/day) or combined with NBUVB (20mg isotretinoin/day+NBUVB). The genotoxic effect was evaluated by the cytokinesis-blocked micronucleus and the comet assays. Our studies showed that isotretinoin alone was not genotoxic when tested in human lymphocytes in vitro and in vivo. There was no clear genotoxic effect in psoriatic patients treated with isotretinoin and NBUVB. The in vitro studies showed that isotretinoin induced apoptosis and necrosis in human lymphocytes at higher doses., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Periods of remission and of exacerbation of psoriatic lesions are common in psoriasis. We recently reported C-reactive protein (CRP) as a marker of psoriasis severity and that some patients still presented with a residual inflammation after treatment. We wondered if this residual inflammation could underlie an earlier exacerbation of psoriasis., Objective: The purpose of our study was to evaluate if there is a relationship between CRP levels, Psoriasis Area and Severity Index (PASI), and body mass index (BMI), at the end of psoriasis treatment, with the length of psoriasis remission., Methods: We followed 46 patients studied at the end of treatment, to record the length of remission; 9 of the patients were treated with topical agents, 17 with narrow-band UVB (NB-UVB), and 20 with psoralen plus UVA (PUVA)., Results: We found that the length of remission correlated with the values for PASI and CRP at the end of therapy. By performing a multiple linear regression analysis, CRP, PASI, and BMI were each significantly associated with length of remission. Patients with residual inflammation at the end of treatment presented with a significantly shorter length of remission. When considering patients grouped according to the used therapies, CRP and PASI also emerged as potential determinants of length of remission, especially in the case of patients treated with NB-UVB and topical therapy., Conclusion: Our data suggest that CRP and PASI are important determinants of length of psoriasis remission for patients treated with phototherapy or topical therapy. Further studies with larger groups of patients are warranted to test this hypothesis. Moreover, we propose that, by the end of the treatment, the evaluation of CRP and PASI could be important to decide, when possible, if the treatment should be continued to achieve lower CRP values and longer periods of remission.

Psoriasis is considered an immune chronic disease in which T cells are accepted as important. Nowadays, it is believed that psoriasis is most likely a T helper (Th)1/Th17 induced inflammatory disease. However, some other cells, such as endothelial cells, dendritic cells, monocytic cells, neutrophils, keratinocytes, and several cytokines, appear to have, at different stages of the disease, an important role in its pathogenesis. For instance, the response to psoriasis therapy is dependent not only on the inactivation of Th1 and Th17 immune responses but also on the inactivation of dendritic cell products. Moreover, interleukin (IL)-23 deregulation appears to be an independent factor in the pathogenesis of psoriasis. Indeed, currently, the IL-23/Th17 axis is believed to be crucial in psoriasis pathogenesis, and its inhibition appears to be important for therapeutic achievement. This review presents the roles and interactions of cells and cytokines that are related to psoriasis pathogenesis., (© 2012 The International Society of Dermatology.)

Background: A few studies in psoriasis vulgaris patients have reported changes suggesting red blood cell (RBC) damage is linked to neutrophil activation, oxidative stress, and psoriasis worsening., Objective: The aim of this study was to evaluate erythroid disturbances in Portuguese psoriasis vulgaris patients, before, during, and after treatment., Methods: A cross-sectional study (n = 73 patients vs 40 healthy control subjects) followed by a longitudinal study (n = 47 patients) was performed, with assessments before, and at 3, 6, and 12 weeks of therapy (10 patients started topical treatment, 17 narrow-band UVB, and 20 photochemotherapy [psoralen plus UVA; PUVA]). Evaluations included hematologic data, total bilirubin levels, membrane-bound hemoglobin (MBH), membrane protein band 3 profile, total plasma antioxidant status (TAS), lipid peroxidation (thiobarbituric acid [TBA] assay), elastase, lactoferrin, and C-reactive protein (CRP)., Results: Before treatment, patients presented with higher leukocyte/neutrophil and reticulocyte counts, elastase, lactoferrin, TBA, TBA/TAS, reticulocyte production index, total bilirubin and MBH values, lower RBC and hematocrit, higher percentages of high-molecular-weight aggregates, and lower percentages of band 3 monomer. After treatment, we observed a reversal in most of the parameters. However, patients still presented with values suggestive of accelerated RBC damage, removal, and production, as most of the parameters were still higher than those in the control group; the same occurred with CRP., Conclusion: Our data suggest that psoriasis vulgaris triggers an inflammatory response, with release of acute-phase reactants, reactive oxygen species, cationic proteins, and proteases, leading to enhanced RBC damage/aging and, ultimately, to enhanced RBC removal. These assumptions were strengthened by the observation that, with treatment, all of these changes were reversed, the inflammation was reduced, the production of reticulocytes was increased, and the RBCs presented changes usually observed in younger/less damaged RBCs. These erythroid changes were enhanced with PUVA therapy, probably due to the more pronounced clearing of the lesions, as suggested by Psoriasis Area and Severity Index (PASI) scores. Finally, after treatment, a residual inflammation still persisted that might contribute to the observed erythroid disturbances.

Background: Psoriasis vulgaris is associated with overweight/obesity and with increased C-reactive protein (CRP), tumour necrosis factor (TNF)-α, interleukin (IL)-6, leptin and resistin levels and decreased adiponectin levels., Objectives: To understand the role/relationship of adipokines, as well as CRP, in a Portuguese psoriatic population, by assessing the relationship of their levels with psoriasis severity, defined by Psoriasis Area and Severity Index (PASI), with obesity, defined by body mass index (BMI), and psoriasis therapy., Methods: A cross-sectional (n=66) and longitudinal study (before and after 12 weeks of therapy; n=44) was performed; 10 patients started topical treatment, 17 narrow-band ultraviolet B (NBUVB) and 17 psolaren associated with UVA (PUVA)., Results: Patients presented significantly higher BMI, leptin, resistin, TNF-α, IL-6 and CRP and significantly lower adiponectin values. CRP and IL-6 correlated with PASI. Adiponectin and leptin were more altered in patients with higher BMI. Concerning severity, CRP, resistin and adiponectin were more altered in the severer forms. After treatment, a significant reduction in PASI, CRP, resistin, TNF-α and IL-6, and a significant rise in adiponectin were observed. Nonetheless, CRP and adiponectin remained different from those of control. Concerning therapies, topical therapy was not associated with any significant change, except for TNF-α. After NBUVB, a significant reduction was observed in TNF-α and in CRP. For PUVA, we observed a significant reduction in TNF-α, IL-6 and CRP, and a significant increase in adiponectin., Conclusion: In psoriatic patients, increased overweight/obesity was associated with raised leptin levels and decreased adiponectin levels. Leptin may contribute to enhance the inflammatory process in overweight/obese psoriatic patients. Resistin, IL-6, CRP and adiponectin levels appear to be dependent on psoriasis severity. CRP, together with IL-6, appears to be a useful marker of psoriasis severity. Both NBUVB and PUVA were effective; however, PUVA results seem to be more successful. Nonetheless, after NBUVB and PUVA, a low-grade inflammation still persists., (© 2010 The Authors. Journal compilation © 2010 European Academy of Dermatology and Venereology.)

Background: Psoriatic patients present with an increased frequency of cardiovascular events., Objective: To study the impact of psoriasis duration and therapy on traditional and new cardiovascular risk factors., Study Design: A longitudinal study performed between 2005 and the first trimester of 2008. Each patient was followed up for 12 weeks, and was observed before and 3, 6, and 12 weeks after starting therapy., Setting: Patients attending the Dermatology Service, University Hospital of Coimbra, Coimbra, Portugal were enrolled., Subjects: Thirty-four patients with psoriasis vulgaris and 37 healthy volunteers as controls., Main Outcome Measures: Psoriasis Area and Severity Index (PASI); lipid profile, oxidized low-density lipoprotein (oxLDL), oxLDL/low-density lipoprotein (LDL), total antioxidant status, lipid peroxidation, C-reactive protein (CRP), and circulating levels of adiponectin., Intervention: Ten patients started therapy with topical treatment, 11 with narrow-band UVB radiation (NB-UVB), and 13 with psolaren plus UVA (PUVA)., Results: Before starting therapy, psoriatic patients presented with several risk changes in their lipid profiles, and significantly higher CRP, oxLDL, and oxLDL/LDL, and lower adiponectin levels (vs control subjects), which may further contribute to inflammation and atherogenesis. After treatment of the patients, although no significant differences were observed in the lipid profile compared with baseline, some changes suggested that the treatment could somehow alter lipid metabolism, as the reduction in high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A and the increase in the atherogenic index cholesterol/HDL-C maintained an even higher significance (as shown by p-values) when compared with the control group. After topical therapy, there was a significant reduction in thiobarbituric acid reactivity only, suggesting that the reduction in the hyperproliferative process within the lesions is important for lipid peroxidation. After NB-UVB therapy, oxLDL/LDL, cholesterol/HDL-C, lipoprotein (a) [Lp(a)], and CRP remained higher than in the control subjects, reflecting persistent inflammation and atherogenic risk. After PUVA treatment, there was a significant reduction in Lp(a), associated with an almost significant increase in apolipoprotein-B (p = 0.054); these changes were not observed after NB-UVB treatment. However, after PUVA and NB-UVB treatment, CRP and, in the NB-UVB group, oxLDL/LDL were persistently higher than controls., Conclusion: Our data show that psoriatic patients present with several lipid profile changes that seem to be related to the severity of the disease and/or the treatment used. Mild psoriasis patients receiving topical treatment presented before starting therapy with a lipid profile similar to controls, whereas those undergoing NB-UVB and PUVA, who had higher PASI scores, presented with several risk factors. Moreover, PUVA therapy seems to interact in a different way with lipids that might result from an interaction of psoralen with plasma lipids, namely Lp(a). Inflammation, a hallmark of psoriasis, also seems to be related to psoriasis severity. Both NB-UVB and PUVA were effective, as shown by the reduction in PASI score, as well as in the oxidative and inflammatory stress markers. However, after NB-UVB and PUVA, a low-grade inflammatory process still persisted, which might be related to the duration of remission of the disease.

Background: Several cross-sectional studies have shown that different cytokines and growth factors are enhanced in psoriasis., Objectives: We aimed to understand the role/relation of interleukin (IL)-22, IL-17, IL-23, IL-8, vascular endothelial growth factor (VEGF) and tumour necrosis factor (TNF)-α in psoriasis vulgaris, addressing their levels and changes before, during and after psoralen-ultraviolet A (PUVA) and narrowband ultraviolet B (NB-UVB) treatment., Methods: A cross-sectional and a longitudinal study (n = 34) - before (T0) and at 3 (T3), 6 (T6) and 12 (T12) weeks of NB-UVB and PUVA therapy - were performed; 17 patients started NB-UVB and 17 PUVA, and IL-22, IL-17, IL-23, IL-8, TNF-α and VEGF levels were evaluated., Results: At T0, compared with controls (n = 20), all the parameters were significantly higher in patients, except for TNF-α. Both NB-UVB and PUVA treatment gave, at T3, a significant decrease in TNF-α and IL-23; IL-22 and IL-17 decreased significantly at T6; all parameters and Psoriasis Area and Severity Index decreased significantly at T12. However, in both groups, at T12, VEGF was still significantly higher than control., Conclusions: Psoriasis seems to be a complex disease in which the cytokine network is disturbed, namely in levels of IL-22, IL-17, IL-23, IL-8, TNF-α and VEGF. NB-UVB and PUVA follow-up studies suggested that the reduction in the IL-23/Th17 axis might be important in the pathogenic mechanisms of psoriasis. Further follow-up studies of patients with psoriasis treated with these and other therapies could be very helpful for the understanding of the disturbance in the cytokine network in psoriasis and indirectly in its pathogenesis., (© 2010 The Authors. BJD © 2010 British Association of Dermatologists.)

Background: Psoriasis vulgaris is a chronic recurrent inflammatory skin disease and psoriatic lesions have shown leucocyte infiltration., Objectives: We aimed to study C-reactive protein (CRP) and leucocyte activation markers/inhibitors as potential monitors of psoriasis vulgaris., Methods: A cross-sectional (n = 73) and a longitudinal study (before, at 3, 6 and 12 weeks of therapy; n = 47) was performed; 10 patients started topical treatment, 17 narrow-band ultraviolet light B (NBUVB) and 20 psolaren associated to UVA (PUVA); psoriasis severity was defined by Psoriasis Area and Severity Index (PASI)., Results: Compared with control (n = 38), we found higher CRP levels, total leukocyte/neutrophil count, elastase, lactoferrin and alpha1-antitrypsin. Increasing PASI was linked to increasing CRP and a trend to higher elastase and lactoferrin, suggesting that worsening enhances inflammatory response with neutrophil activation. CRP correlated with PASI, total leucocytes, neutrophils, elastase, lactoferrin and alpha1-antitrypsin. NBUVB and PUVA presented similar effects., Conclusion: We propose CRP as a useful marker of psoriasis severity that could be used to monitor psoriasis and its treatment, and, together with PASI and elastase, could also be used as a global index of severity.

Background: Psoriasis is a chronic and recurrent inflammatory skin disease. The inflammatory response represents a fundamental ability of the organism to protect itself from infectious agents and from injury., Objectives: To evaluate the inflammatory response in mild and in severe psoriasis, to evaluate the endogenous systems counterbalancing the deleterious effects of the inflammation products, and to establish values of prognostic significance., Methods: The study was performed in a control group (n = 40) and in 60 patients with psoriasis vulgaris, half presenting with mild psoriasis, and the other half with severe psoriasis. We evaluated total and differential leucocyte count; elastase, lactoferrin and lipid peroxidation as markers of neutrophil activation; total plasma antioxidant capacity (TAS), transferrin, ceruloplasmin, alpha(1)-antitrypsin and alpha(2)-macroglobulin as markers of the endogenous antioxidant and antiprotease systems; and fibrinogen, erythrocyte sedimentation rate, C-reactive protein (CRP), haptoglobin, C3 and C4 complement proteins as markers of inflammation., Results: Our data suggested that psoriasis is an inflammatory condition in which neutrophils seem to play a crucial role by contributing to the development of oxidative and proteolytic stress. The worsening of the disease seemed to be linked to the enhancement of the inflammatory response and of the imbalance between neutrophil activation products and their inhibitors., Conclusions: We propose values for elastase, CRP, elastase/alpha(2)-macroglobulin, elastase/alpha(1)-antitrypsin, thiobarbituric acid/TAS and elastase/neutrophil ratios with prognostic significance for the worsening of psoriasis.

Background: Psoriasis is a common chronic and recurrent inflammatory skin disorder. Oxygen metabolites and proteases released by activated inflammatory cells may induce oxidative and proteolytic damage to plasma constituents and red blood cells (RBCs). RBCs have a limited biosynthesis capacity and poor repair mechanisms., Objectives: To study RBCs as a potential cumulative marker of oxidative and proteolytic stress in psoriasis, and as a marker of worsening of the disease., Methods: The study was performed in 70 patients with mild or severe psoriasis and in 40 control individuals. We evaluated total and differential leucocyte count and, as markers of leucocyte activation, plasma elastase and lactoferrin. Besides the basic RBC study (RBC count, haematocrit, haemoglobin concentration and haematimetric indices) we evaluated antioxidant defences (catalase, superoxide dismutase, glutathione peroxidase and selenium), osmotic fragility and reticulocyte count; in the RBC membrane we evaluated lipid peroxidation and susceptibility to lipid peroxidation, membrane fluidity, levels of cholesterol and phospholipids, membrane-bound haemoglobin, band 3 profile and levels of vitamin E; serum levels of bilirubin, total plasma antioxidant capacity, lipid profile and lipid peroxidation were also evaluated., Results: Psoriasis patients showed a rise in leucocytes, mainly neutrophils, which was associated with a rise in elastase and lactoferrin. Patients had a reduced RBC count, antioxidant defences and membrane fluidity, elevated membrane lipid peroxidation, membrane-bound haemoglobin, osmotic fragility and reticulocyte count, and a different band 3 profile. Most of these modifications were enhanced in severe psoriasis., Conclusions: In summary, our data show that the RBCs are at a lower number in psoriasis patients, and present several changes denoting an enhanced damage and/or ageing process, which seem to be strongly connected with neutrophil activation, oxidative stress and worsening of psoriasis.

Psoriasis is a common chronic and recurrent inflammatory skin disorder that has been associated with oxidative stress, abnormal plasma lipid metabolism and with high frequency of cardiovascular events. This prevalence seems to be related to the severity of psoriasis, as it occurs more frequently in patients presenting large areas of the body affected with psoriasis lesions. The aim of our work was to evaluate the development of oxidative stress and of dislipidemia in psoriasis, and to look for a correlation between their levels and worsening of psoriasis. We evaluated lipid profile, total antioxidant capacity, antioxidant vitamins A and E, and lipoperoxidation products. The study was performed in controls and in patients presenting mild and severe psoriasis. Patients presented risk changes in lipid profile (a rise in cholesterol (P<0.01), triglycerides (P<0.001), low density lipoprotein cholesterol (P<0.01), very low density lipoprotein cholesterol (P<0.01), apolipoprotein B (P<0.001) and lipoprotein(a) (P<0.001); and a reduction in high density lipoprotein cholesterol (P<0.001)), a rise in lipoperoxidation products (P<0.001) and a reduction in total antioxidant capacity (P<0.001) and in antioxidant vitamins A (P<0.001) and E (P<0.05). Moreover, we found that the worsening of psoriasis was associated with the enhancement of oxidative stress and of the lipid risk changes. Our data suggest that psoriasis patients must be considered as a group at risk for cardiovascular disease and that this risk seems to be higher in severe psoriasis. In addition, a possible benefit of an enriched diet or of a supplement of vitamins A and E in psoriasis patients should be further studied.