Dorota Krasowska

Cytokines and anticytokines in psoriasis.

BACKGROUND Psoriasis is a chronic autoimmune hyperproliferative skin disease of varying severity affecting approximately 2-3% of the general population in the USA and Europe. Although the pathogenesis of psoriasis has not been fully elucidated, an immunologic-genetic relationship is likely. Cutaneous and systemic overexpression of various proinflammatory cytokines (TNF, interleukins, interferon-gamma) has been demonstrated in psoriatic patients. METHODS We reviewed the current database literature and summarized the involvement of cytokines and their receptors in the pathogenesis and treatment of psoriasis. RESULTS Although many cytokine/anti-cytokine therapies have been conducted, TNF antagonists in the treatment of both psoriasis arthropatica and vulgaris appear to be the most widely used clinically. Interestingly, the efficacy and tolerability of some cytokines (rhIL-11 or ABX-IL-8,) were found to be much lower than expected. CONCLUSIONS Preliminary results obtained with cytokine and anti-cytokine therapies appear promising and as such continued research is clearly indicated.

Lack of association between three vascular endothelial growth factor gene polymorphisms and systemic sclerosis: results from a multicenter EUSTAR study of European Caucasian patients

Introduction: Systemic sclerosis (SSc) is characterised by disturbed vessel morphology and an overproduction of vascular endothelial growth factor (VEGF). The VEGF gene located on chromosome 6p21.3 has several polymorphisms. Objective: To test the hypothesis that disturbed angiogenesis may be related to the genetic background of the VEGF gene. Materials and methods: EUSTAR centres included European Caucasian patients with SSc and matched controls with osteoarthritis. The VEGF gene was genotyped by polymerase chain reaction, followed by restriction enzyme analysis. The 634 C/T and 936 C/G mutations and an 18-base pair insertion/deletion at −2549 of the VEGF promoter region were tested. Results: 416 patients with SSc and 249 controls were included in the study population. Of the patients with SSc, 42% had a diffuse cutaneous subtype, 16% had increased pulmonary arterial pressure and 61% had decreased carbon monoxide diffusion capacity. The genotype frequencies in the patients with SSc and in controls were in Hardy–Weinberg equilibrium. The allele and genotype frequencies of the polymorphisms did not differ between patients with SSc and controls. No association was found between these polymorphisms and disease phenotypes. Conclusion: This study shows that there is no association between the three selected functional VEGF polymorphisms and SSc.

Outcomes of Barrett’s oesophagus related to systemic sclerosis: a 3-year EULAR Scleroderma Trials and Research prospective follow-up study

OBJECTIVE Barretts oesophagus (BE) is the major risk factor for oesophageal adenocarcinoma (EAC). SSc is associated with an increased risk of BE related to chronic reflux. The aim of this study is to determine the outcomes of BE and estimate the EAC risk in SSc patients over a 3-year prospective study. METHODS SSc patients were recruited through EUSTAR network centres. Inclusion criterion was a recent histological finding of BE. The patients were then prospectively followed and, as recommended, a second oesophageal endoscopy was performed according to the presence of BE-related dysplasia at baseline. RESULTS A total of 50 SSc patients with BE (40 without and 10 with dysplasia) were included and 46 completed the follow-up (138 patient-years). During the 3-year follow-up, 4 of the 46 BE patients (3% per year) were diagnosed with high-grade dysplasia/EAC, of which one developed cardial EAC. EAC incidence in the BE subgroup with dysplasia increased to 4% per year compared with the absence of EAC cases in the BE subgroup without dysplasia at baseline. CONCLUSION Our results, in accordance with previous published data suggesting an increased risk of EAC or cardial adenocarcinoma in SSc, highlight the need for accurate follow-up of BE SSc patients at risk of developing adenocarcinoma.

Social support and adaptation to the disease in men and women with psoriasis

Social support was shown to be an important factor buffering negative effects of stress in a range of clinical populations. Little is known, however, about the role of social support in the population of patients with psoriasis although strong psychosocial stress has been implicated in this disease. The objective of this study was to evaluate the association between social support and selected indices of adaptation to life with the disease, including health-related quality of life, depressive symptoms and acceptance of life with the disease, in a sample of patients with psoriasis. Additionally, gender differences in these relationships were analyzed. One-hundred-four patients with psoriasis completed psychological tests measuring disease-related social support, health-related quality of life, depressive symptoms and acceptance of life with the disease. Psoriasis severity was assessed by Psoriasis Area and Severity Index. The patients reporting higher social support levels had significantly higher quality of life, lower depression levels, and higher acceptance of life with the disease. The strengths of these effects, however, were different in women and men. Higher social support was slightly more closely associated with better acceptance of life with the disease in men than in women. However, higher social support was more closely associated to lower depression and better quality of life in women than in men. Among different types of social support, tangible support was found to be the best predictor for the all adaptation indices. Effects of social support perceived by psoriasis patients on adaptation to the disease may be gender-related and exact pathways of these effects may depend on the type on the dimension of social support and the selected type of adaptation indicator. Tangible support seems the most important type of support contributing to better adaptation in both women and men with psoriasis.

High serum sCD163/sTWEAK ratio is associated with lower risk of digital ulcers but more severe skin disease in patients with systemic sclerosis

IntroductionSystemic sclerosis (SSc) is an autoimmune disease characterized by chronic inflammation, vascular injury and excessive fibrosis. CD163 is a scavenger receptor which affects inflammatory response and may contribute to connective tissue remodelling. It has recently been demonstrated that CD163 can bind and neutralize the TNF-like weak inducer of apoptosis (TWEAK), a multifunctional cytokine which regulates inflammation, angiogenesis and tissue remodelling. We aimed to investigate the relationships between serum levels of soluble CD163 (sCD163) and soluble TWEAK (sTWEAK) in relation to disease manifestations in SSc patients.MethodsThis study included 89 patients with SSc who had not received immunosuppressive drugs or steroids for at least 6 months and 48 age- and sex-matched healthy controls (HC) from four European centres. Serum concentrations of sTWEAK and sCD163 were measured using commercially available ELISA kits.ResultsThe mean serum concentrations of sTWEAK were comparable between SSc patients (mean +/- SD: 270 +/- 171 pg/mL) and HC (294 +/- 147pg/mL, P >0.05). Concentration of sCD163 and sCD163/sTWEAK ratio were significantly greater in SSc patients (984 +/- 420 ng/mL and 4837 +/- 3103, respectively) as compared to HC (823 +/- 331 ng/mL and 3115 +/- 1346 respectively, P <0.05 for both). High sCD163 levels and a high sCD163/sTWEAK ratio (defined as > mean +2SD of HC) were both associated with a lower risk of digital ulcers in SSc patients (OR, 95%CI: 0.09; 0.01, 0.71, and 0.17; 0.06, 0.51, respectively). Accordingly, patients without digital ulcers had a significantly higher sCD163 concentration and sCD163/sTWEAK ratio as compared to SSc patients with digital ulcers (P <0.01 for both) and HC (P <0.05 for both). A high sCD163/sTWEAK ratio, but not high sCD163 levels, was associated with greater skin involvement.ConclusionsThe results of our study indicate that CD163-TWEAK interactions might play a role in the pathogenesis of SSc and that CD163 may protect against the development of digital ulcers in SSc. Further studies are required to reveal whether targeting of the CD163-TWEAK pathway might be a potential strategy for treating vascular disease and/or skin fibrosis in SSc.

Generalized lichenoid drug eruption following Blaschko lines

A 16‐year‐old girl was referred for evaluation of a widespread rash of 1 month duration. Its onset was on the trunk, but it rapidly generalized to cover virtually the entire body. It was intensely pruritic. The girl had a history of recurrent frontal headaches and had been taking ibuprofen 1 month prior to and during the onset of the rash. She was in otherwise good health.

Psoriasis and serum lipid abnormalities

Psoriasis affects approximately 120–180 million people worldwide. Interestingly, its incidence increased significantly from 50.8 in the period 1970–1974 to 100.5 per 100,000 in the period 1995– 1999 (1). In recent years, pathophysiological phenomena in psoriasis and disease-related psychosocial aspects have been approached quite differently. The multiaspect nature of psoriasis as a systemic disease associated with numerous multiorgan abnormalities and complications has been recognized. The available studies indicate that the etiology of psoriasis may be extremely diverse in individual patients. It is known that its prevalence in the population is affected by genetic, environmental, immunological, viral, infectious, biochemical, endocrine, and psychological (trauma, stress) factors as well as alcohol and drug abuse (2,3). Psoriasis is associated with cardiovascular abnormalities; moreover, it increases the risk of the numerous diseases, including atherosclerosis, metabolic syndrome, dyslipidemia, hypertension, diabetes type 2, obesity, cancer, depression, osteoporosis, chronic obstructive pulmonary disease, and even cerebral stroke (4,5,6). The knowledge concerning new parameters involved in the psoriatic process increases continuously. The recent findings presented by Chen and coworkers (2009) (3) demonstrate elevated levels of osteopontins (OPNs) in peripheral blood of psoriatic patients. According to them, high levels of OPNs in plasma are unfavorable risk factors of cardiovascular diseases in psoriatic patients. It should be stressed that the regulation of cellular cholesterol metabolism is fully shaped already in the fetal life. The maintenance of its steady cellular levels is an important element of cellular and systemic homeostasis (7). Alterations in the organization of lipids may lead to serious consequences affecting such cellular functions as signal transduction and membrane trafficking (8). The main features of the corneous layer observed under scanning electron microscope include widened intracellular spaces, lack of resistant intercellular junctions, and impaired intracellular adhesion, which may result in markedly abnormal cholesterol homeostasis (8,9). This phenomenon may be reflected by other lipid metabolism disturbances in psoriasis. Cholesterol is one of the essential regulators of lipid organization, and mammals have developed sophisticated mechanisms to maintain low cellular cholesterol levels in membranes. As soon as these homeostatic mechanisms are overwhelmed, as in late stages of atherosclerosis, the results can be very dangerous (8). The objective of the present study is to review the available literature data on lipid metabolism abnormalities in psoriasis, relations of such abnormalities with systemic changes, and effects of lipid diet on psoriasis together with drugs’ influence on lipid parameters. In 1924 Ishimaru, one of the pioneers of lipid metabolism research in psoriasis, quantitavely analyzed serum cholesterol in psoriatic patients. However, his findings were not conclusive. In subsequent years, numerous researchers addressed this issue. Lortat–Jacob and coworkers (1926) were the first to pay attention to hypercholesterolemia in psoriatic patients and possible alleviation of disease clinical symptoms by decreasing cholesterol levels (10,11). In the same year, Lacroix demonstrated significant amount of cholesterol in scaly plagues. He detected elevated cholesterol levels in serum – in 40% of patients, this index was higher than 200 mg % – and suggested that psoriasis might be the form of cholesterol elimination through the skin (10). In the 30s, Grutz and Burger considered psoriasis as “lipoidosis” and put forward the hypothesis that the intestinal epithelial cells, like psoriatic keratinocytes, contained excessive lipids, which is likely to hinder the absorption of lipids through the intestinal wall. They considered the development

Serum level of sELAM-1 in psoriatic patients correlates with disease activity

Endothelial leucocyte adhesion molecule‐1 (ELAM‐1) acts as an adhesion ligand for neutrophils and monocytes and the expression of this molecule on the vascular endothelium may reflect its ability to recruit neutrophils from circulation. The next step is the transendothelial migration of neutrophils into lesional psoriatic skin. ELAM‐1 may also exist in a soluble form.

European dermatology forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 2: Scleromyxedema, scleredema and nephrogenic systemic fibrosis

The term ‘sclerosing diseases of the skin’ comprises specific dermatological entities which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first‐ and advanced‐line therapy of sclerosing skin diseases are addressed in detail. Part 2 of this guideline provides clinicians with an overview of the diagnosis and treatment of scleromyxedema, scleredema (of Buschke) and nephrogenic systemic sclerosis (nephrogenic fibrosing dermopathy).

Depressiveness, measured with Beck Depression Inventory, in patients with psoriasis

BACKGROUND The aim of this study was to identify demographic and clinical factors predisposing to depressiveness during the course of psoriasis. METHOD The study included 239 patients with psoriasis (15-76 years, 31.8% of women) and 123 healthy controls (17-74 years, 32.5% of women). Dependent variable in the analysis was Beck Depression Inventory (BDI) score. Explanatory variables included: age, sex, marital status, education, occupational activity, body mass index (BMI), systolic and diastolic blood pressure, history of smoking, average number of smoked cigarettes, skin lesions visible to others, comorbidities, including arterial hypertension and arthritis, number of previous hospitalizations and family history of psoriasis. RESULTS Psoriatics showed higher BDI scores than the controls, and significantly more often presented with depressiveness. Depressiveness correlated with psoriasis, older age, female sex, lack of higher education, occupational inactivity, higher BMI, visible skin lesions, comorbidities, including arterial hypertension and arthritis, greater number of previous hospitalizations and lack of family history of psoriasis. Multivariate analysis showed than independent predictors of any grade depressiveness were psoriasis (OR=2.26, 95%CI: 1.11-4.60, p=0.024), older age (OR=1.03, 95%CI: 1.01-1.05, p=0.005) and female sex (OR=2.73, 95%CI: 1.45-5.12, p=0.002). LIMITATIONS Cross-sectional, non-prospective analysis. Selection bias. CONCLUSIONS Patients with psoriasis, irrespective of its severity and related complications, are at increased risk of depressiveness. The risk of secondary depressiveness is particularly high in psoriatic women and older persons (or individuals diagnosed with psoriasis at younger age). Individuals from this group should be monitored for potential depressive symptoms.