Américo Figueiredo

The inflammatory response in mild and in severe psoriasis

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.

Dislipidemia and oxidative stress in mild and in severe psoriasis as a risk for cardiovascular disease

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.

Interleukin (IL)-22, IL-17, IL-23, IL-8, vascular endothelial growth factor and tumour necrosis factor-α levels in patients with psoriasis before, during and after psoralen-ultraviolet A and narrowband ultraviolet B therapy.

Background  Several cross‐sectional studies have shown that different cytokines and growth factors are enhanced in psoriasis.

C-reactive protein and leucocyte activation in psoriasis vulgaris according to severity and therapy

Background  Psoriasis vulgaris is a chronic recurrent inflammatory skin disease and psoriatic lesions have shown leucocyte infiltration.

Circulating adipokine levels in Portuguese patients with psoriasis vulgaris according to body mass index, severity and therapy

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.

Epicutaneous patch testing in drug hypersensitivity syndrome (DRESS)

Background: In some patterns of cutaneous adverse drug reactions, and depending on the culprit drug, patch testing has been helpful in confirming its cause. Its value in Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) has not been established in a large cohort of patients.

The roles of cells and cytokines in the pathogenesis of psoriasis

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.

Granulocyte-macrophage colony-stimulating factor activates the transcription of nuclear factor kappa B and induces the expression of nitric oxide synthase in a skin dendritic cell line

Nitric oxide (NO) produced by skin dendritic cells and keratinocytes plays an important role in skin physiology, growth and remodelling. Nitric oxide is also involved in skin inflammatory processes and in modulating antigen presentation (either enhancing or suppressing it). In this study, we found that GM‐CSF stimulates the expression of the inducible isoform of nitric oxide synthase (iNOS) in a fetal‐skin‐derived dendritic cell line (FSDC) and, consequently, increases the nitrite production from 11.9 ± 3.2 μmol/L (basal level) to 26.9 ± 4.2 μmol/L. Pyrrolidinedithiocarbamate (PDTC) inhibits nitrite production, with a half maximal inhibitory concentration (IC50) of 19.3 μmol/L and the iNOS protein expression in FSDC. In addition, western blot assays revealed that exposure of FSDC to GM‐CSF induces the phosphorylation and degradation of the inhibitor of NF‐κB (IkB), with subsequent translocation of the p50, p52 and RelB subunits of the transcription nuclear factor kappa B (NF‐κB) from the cytosol to the nucleus. Electrophoretic mobility shift assays (EMSA) showed that FSDC exposure to GM‐CSF activates the transcription factor NF‐κB. Together, these results show that GM‐CSF induces iNOS expression in skin dendritic cells by a mechanism involving activation of the NF‐κB pathway.

Contact sensitizer nickel sulfate activates the transcription factors NF-kB and AP-1 and increases the expression of nitric oxide synthase in a skin dendritic cell line

Abstract:  Nuclear factor kappa B (NF‐kB) and activating protein‐1 (AP‐1) transcription factors are ubiquitously expressed signaling molecules known to regulate the transcription of a large number of genes involved in immune responses, namely the inducible isoform of nitric oxide synthase (iNOS). In this study, we demonstrate that a fetal skin‐derived dendritic cell line (FSDC) produces nitric oxide (NO) in response to the contact sensitizer nickel sulfate (NiSO4) and increases the expression of the iNOS protein, as determined by immunofluorescence and Western blot analysis. The sensitizer NiSO4 increased cytoplasmic iNOS expression by 31.9 ± 10.3% and nitrite production, as assayed by the Griess reaction, by 27.6 ± 9.5%. Electrophoretic mobility shift assay (EMSA), showed that 30 min of FSDC exposure to NiSO4 activates the transcription factor NF‐kB by 58.2 ± 7.0% and 2 h of FSDC exposure to NiSO4 activates the transcription factor AP‐1 by 26.0 ± 1.4%. Together, these results indicate that NiSO4 activates the NF‐kB and AP‐1 pathways and induces iNOS expression in skin dendritic cells.

Photosensitivity to piroxicam: absence of cross‐reaction with tenoxicam

We studied 2 groups of patients. One group or 10 patients had a photosensitive eruption to piroxicam. Another group of 24 patients had positive patch test reactions to thimerosal and thiosalicylie acid and had never taken piroxicam or tenoxicam. Patients were patch tested with thimerosal 0.1% pet., thiasalicylic acid 0.1% pet., salicylic acid 2.0% pet., piroxicam 1 and 5% pet. and tenoxicam 1 and 5% pet. photopatch tests were also performed with piroxicam and tenoxicam. All 10 patients with photosensitivity to piroxicam had positive patch tests to thiosalicylic and thiosalicylic acid and 9 of them had positive photopatch tests to ptroxicam. 20 out of 24 patients with positive patch tests to thiosalicylic acid also had positive photopatch tests to Piroxicam. All the patients tested with salicylic add were negative. Out of the 29 patients with positive photopatch tests to piroxicam, none reacted to tenoxicam. In countries with a high incidence of contact sensitivity to thimerosal/thiosalicylic acid, the use of piroxicam should be avoided and replaced by tenoxicam, a drug without reported photosensitivity