Psoriasis severity and hypothalamic-pituitary-adrenal axis function: results from the CALIPSO study

Psoriasis is a chronic inflammatory disease that significantly impacts life quality, being associated with stress and mental disorders. We investigated whether the activity of the hypothalamic-pituitary-adrenal (HPA) axis was associated with psoriasis severity, daily life stress and anxiety, and depressive symptoms. In this ancillary study, which was part of the CALIPSO (coronary artery calcium in psoriasis) study, saliva was collected from 102 patients with psoriasis immediately upon awakening, 30, and 60 min after awakening, at 2:00 pm and at bedtime (five time points) to determine salivary cortisol levels. We used Pearson's correlation coefficient to evaluate the association of clinical and psychopathological variables with HPA activity. We found a direct correlation between bedtime cortisol and psoriasis severity evaluated by the psoriasis area severity index (PASI; r=0.39, P<0.001). No correlations between other clinical and psychopathological variables or with other cortisol assessments were observed. The findings indicated that HPA dysfunction may be present in psoriasis, as bedtime cortisol was correlated with psoriasis severity. Our study is limited by the lack of a control group; therefore, we were not able to explore whether these cortisol values were different compared with a concurrent, healthy sample.

Decreased brain-derived neurotrophic factor plasma levels in psoriasis patients

Brain-derived neurotrophic factor (BDNF) is associated with neuroplasticity and synaptic strength, and is decreased in conditions associated with chronic stress. Nevertheless, BDNF has not yet been investigated in psoriasis, a chronic inflammatory systemic disease that is exacerbated by stress. Therefore, our aim was to determine BDNF plasma levels in psoriasis patients and healthy controls. Adult patients (n=94) presenting with psoriasis for at least 1 year were enrolled, and age- and gender-matched with healthy controls (n=307) from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Participants had neither a previous history of coronary artery disease nor current episode of major depression. BDNF plasma levels were determined using the Promega ELISA kit. A general linear model was used to compare BDNF levels in psoriasis patients and controls, with age, gender, systolic blood pressure, serum fasting glucose, blood lipid levels, triglycerides, smoking status, and body mass index examined. After adjusting for clinical and demographic variables, significantly decreased BNDF plasma levels were observed in psoriasis patients (P=0.01) (estimated marginal means of 3922 pg/mL; 95%CI=2660-5135) compared with controls (5788 pg/mL; 95%CI=5185-6442). Similar BDNF levels were found in both mild and severe cases of psoriasis. Our finding, that BDNF is decreased in psoriasis, supports the concept of a brain-skin connection in psoriasis. Further studies should determine if BDNF is increased after specific psoriasis treatments, and associated with different disease stages.

Economic Burden of Psoriasis

Psoriasis may cause a substantial economic burden to patients, health service providers, third parties, and the society as a whole. However, all of these costs may not be adequately considered when assessing the treatment costs for psoriasis. Psoriasis may negatively affect work productivity as psoriasis has a relatively high incidence in working age people that lead to possible costs because of lost productivity. The aims of this thesis were to estimate the economic burden of psoriasis particularly from patients’ and health service providers’ perspectives and to estimate the background factors (e.g., severity of psoriasis) that may have led to high costs. Another aim was to estimate the total medication costs and to estimate psoriasis’ proportion of health-related productivity losses. The patient sample was based on patients with psoriasis who visited the Department of Dermatology in Turku University Hospital during a one-year study period. These patients were sent a questionnaire. From the patients who gave consent, medication information, clinical information, and number of visits to Turku University Hospital were collected. This data was linked to the information from the questionnaire. Overall psoriasis was estimated to cause a substantial economic burden for the patient, health service provider, health insurance system, employer, and the society as a whole. The direct costs represented only a small proportion of the overall financial burden of psoriasis, whereas indirect costs were significant. The estimated annual costs for patients and employers were almost twice the costs to health service providers or the Social Insurance Institution of Finland. In conclusion, the cost contribution of patients and employers should be considered when assessing the costs of different treatments, in addition to commonly studied direct costs of medications and costs to health service providers. Methods used to assess these costs should be well justified and be described clearly to allow comparisons between studies and to evaluate the quality of the results.

The use of relaxation therapy as an adjunct to traditional psoriasis therapy /

This research investigated the impact of stress management and relaxation techniques on psoriasis. It had a dual purpose to see if stress management and relaxation techniques, as an adjunct to traditional medical treatment, would improve the skin condition of psoriasis. In addition it attempted to provide psoriasis patients with a sense of control over their illness by educating them about the connection between mind and body through learning stress management and relaxation techniques. The former purpose was addressed quantitatively, while the latter was addressed qualitatively. Using an experimental design, the quantitative study tested the efficacy of stress management and relaxation techniques on 38 dermatological patients from St. John's, Newfoundland. The study which lasted ten weeks, suggested a weak relationship between psoriasis and stress. These relationships were not statistically significant. The qualitative data were gathered through unstructured interviews and descriptive/interpretative analysis was used to evaluate them. Patients in the experimental group believed in the mind body connection as it related to their illness and stress. The findings also showed that the patients believed that the stress reduction and relaxation techniques improved their quality of life, their level of psoriasis, and their ability to live with the condition. Based on the contradictory nature of the findings, further research is needed. It is posited that replication of this study would be vastly improved by increasing the sample size to increase the possibility of significant findings. As wel~ increasing the length of time for the experiment would control for the possibility of a lag effect. Finally, the study looked at linear relationships between stress and psoriasis. Further study should ascertain whether the relationship might be nonlinear

Asociación entre psoriasis y el control de diabetes mellitus tipo 2

La psoriasis es una enfermedad que se caracteriza por un proceso inflamatorio crónico y exagerado local y sistémico. Se ha encontrado en la literatura una relación entre la psoriasis y el desarrollo de patologías como diabetes mellitus tipo 2 y el mal control de estas patologías, lo cual aumenta la morbimortalidad de estos pacientes. El presente estudio mostró que no se encontró asociación entre psoriasis y el control de la DM2 , y que la variable mas significativa sobre el control es la adherencia al tratamiento hipoglicemiante.

Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis

Background: Cannabinoids from cannabis (Cannabis sativa) are anti-inflammatory and have inhibitory effects on the proliferation of a number of tumorigenic cell lines, some of which are mediated via cannabinoid receptors. Cannabinoid (CB) receptors are present in human skin and anandamide, an endogenous CB receptor ligand, inhibits epidermal keratinocyte differentiation. Psoriasis is an inflammatory disease also characterised in part by epidermal keratinocyte hyper-proliferation. Objective: We investigated the plant cannabinoids Delta-9 tetrahydrocannabinol, cannabidiol, cannabinol and cannabigerol for their ability to inhibit the proliferation of a hyper-proliferating human keratinocyte cell line and for any involvement of cannabinoid receptors. Methods: A keratinocyte proliferation assay was used to assess the effect of treatment with cannabinoids. Cell integrity and metabolic competence confirmed using lactate-dehydrogenase and adenosine tri-phosphate assays. To determine the involvement of the receptors, specific agonist and antagonist were used in conjunction with some phytocannabinoids. Western blot and RT-PCR analysis confirmed presence of CB1 and CB2 receptors. Results: The cannabinoids tested all inhibited keratinocyte proliferation in a concentration-dependent manner. The selective CB2 receptor agonists JWH015 and BML190 elicited only partial inhibition, the non-selective CB agonist HU210 produced a concentration-dependent response, the activity of theses agonists were not blocked by either C81 /C82 antagonists. Conclusion: The results indicate that while CB receptors may have a circumstantial role in keratinocyte proliferation, they do not contribute significantly to this process. Our results show that cannabinoids inhibit keratinocyte proliferation, and therefore support a potential role for cannabinoids in the treatment of psoriasis. (c) 2006 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Design, synthesis and in vitro degradation of a novel co-drug for the treatment of psoriasis

Psoriasis is a common, chronic and relapsing inflammatory skin disease. It affects approximately 2% of the western population and has no cure. Combination therapy for psoriasis often proves more efficacious and better tolerated than monotherapy with a single drug. Combination therapy could be administered in the form of a co-drug, where two or more therapeutic compounds active against the same condition are linked by a cleavable covalent bond. Similar to the pro-drug approach, the liberation of parent moieties post-administration, by enzymatic and/or chemical mechanisms, is a pre-requisite for effective treatment. In this study, a series of co-drugs incorporating dithranol in combination with one of several non-steroidal anti-inflammatory drugs, both useful for the treatment of psoriasis, were designed, synthesized and evaluated. An ester co-drug comprising dithranol and naproxen in a 1:1 stoichiometric ratio was determined to possess the optimal physicochemical properties for topical delivery. The co-drug was fully hydrolyzed in vitro by porcine liver esterase within four hours. When incubated with homogenized porcine skin, 9.5% of the parent compounds were liberated after 24 h, suggesting in situ esterase-mediated cleavage of the co-drug would occur within the skin. The kinetics of the reaction revealed first order kinetics, Vmax = 10.3 μM/min and Km = 65.1 μM. The co-drug contains a modified dithranol chromophore that was just 37% of the absorbance of dithranol at 375 nm and suggests reduced skin/clothes staining. Overall, these findings suggest that the dithranol-naproxen co-drug offers an attractive, novel approach for the treatment of psoriasis.

Infliximab-induced psoriasis during therapy for Crohn's disease

Although therapy with tumor necrosis factor-alpha inhibitors (anti-TNF) provides beneficial effects in different immune inflammatory disorders, paradoxical cases of anti-THE-induced psoriasis have increasingly been reported, mostly in the setting of rheumatologic diseases. To date, less than 50 cases of infliximab-induced psoriasis in inflammatory bowel disease patients have been described. The present report was aimed at describing two new cases of infliximab-induced psoriasis during therapy for Crohn's disease and at carrying out a review on this intriguing phenomenon. (C) 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Expression of human leucocyte antigen-G primarily targets affected skin of patients with psoriasis

P>BackgroundThe nonclassical human leucocyte antigen (HLA)-G molecule has been well recognized as a tolerogenic molecule and few studies have evaluated the role of the molecule in inflammatory cutaneous autoimmune diseases.ObjectivesTo evaluate the expression of HLA-G in skin specimens of patients with psoriasis and to analyse its correlation with epidemiological and clinical variables.MethodsThirty untreated patients with psoriasis and 32 healthy individuals were enrolled. Immunohistochemistry was applied to identify HLA-G expression in formalin-fixed paraffin-embedded cutaneous skin biopsies.ResultsSoluble and membrane-bound HLA-G expression was detected in 30 (90%) of the skin specimens from patients presenting clinical and histopathological features of psoriasis. Although infiltrating lymphomononuclear cells of the dermis exhibited HLA-G expression, the epidermis was primarily targeted. HLA-G expression was also observed in 27% (three of 11) of the specimens that exhibited no clinical and histopathological features of psoriasis (nonaffected areas). In contrast, skin specimens obtained from healthy individuals exhibited no HLA-G expression (P < 0 center dot 0001). The intensity of HLA-G expression was not associated with type I/II psoriasis, Psoriasis Area and Severity Index score or clinical forms.ConclusionsAs the HLA-G molecule was consistently expressed in affected and, to a lesser extent, in nonaffected areas of untreated patients with psoriasis, irrespective of the severity of the clinical variants, one may hypothesize that the presence of HLA-G may be responsible, at least in part, for the regulation of autoimmune effector cells.

Both psoriasis and benign migratory glossitis are associated with HLA-Cw6

This study was undertaken to investigate human leucocyte antigen (HLA) associations with benign migratory glossitis and psoriasis in Brazilian patients and particularly to determine whether benign migratory glossitis is also associated with HLA-Cw6, the classical association observed in psoriasis. The results showed a highly significant association of Cw6 with both psoriasis and benign migratory glossitis, with this antigen being present in 59.% of the patients with psoriasis, in 43.8% of the patients with benign migratory glossitis, and in only 12.6% of the controls. Other significant positive associations, although at a lower significance level, were with B13, both in psoriasis and in benign migratory glossitis, and with B17, only in psoriasis. To our knowledge, this is the first report on the association of Cw6 with benign migratory glossitis. We believe that this finding reinforces the concept of a pathogenetic relationship between benign migratory glossitis and psoriasis.