The A/A genotype of an interleukin-17A polymorphism predisposes to increased severity of atopic dermatitis and coexistence with asthma.

INTRODUCTION: Studies have found that the interleukin-23/T helper 17 (IL-23/Th17) pathway plays an important role in the pathogenesis of atopic dermatitis (AD). Inhibition of the IL-23/Th17 pathway with monoclonal antibodies reduces skin inflammation in animal models. AIM: To investigate the association between IL-17A and IL-23R gene single nucleotide polymorphisms (SNPs) and the development of AD in a Polish population. METHODS: Blood samples were collected from 166 patients with AD and 160 controls. We analyzed two SNPs, -152 G/A IL-17A and 1142 G/A IL-23R, using PCR and restriction fragment length polymorphism (RFLP) analysis. RESULTS: There was no statistically significant difference between the examined IL-17A SNP and the incidence of AD (P > 0.05 for all comparisons). Analysis of the IL-23R gene SNP showed no relationship between AD and the G/A genotype or presence of the A allele. The study did not establish any links between the IL-23R and IL-17A gene SNPs and the likelihood of developing AD resulting from gene-gene interaction. However, there was a significant relationship between the A/A genotype in the -152 G/A IL1-7A SNP and the coexistence of AD and asthma (P < 0.04). Analyzing the association between AD severity and the occurrence of IL-17A SNP, we found that subjects with the A/A genotype were at higher risk of developing moderate or severe AD (P = 0.02). CONCLUSIONS: We found no evidence of any effect of IL-17A or IL-23R SNPs on the occurrence of AD in our Polish population. However, the A/A genotype in IL-17A was found to predispose to increased AD severity and coexistence of AD and asthma.

Exacerbations of bipolar disorder triggered by chloroquine in systemic lupus erythematosus--a case report.

Despite precise definitions and exclusions for 19 syndromes of neuropsychiatric systemic lupus erythematosus (NPSLE), under some circumstances it appears to be difficult to differentiate whether neuropsychiatric symptoms are caused by SLE or by other reasons such as primary mental disorders or substance-induced mood disorders, especially induced by glucocorticoids or antimalarials. We report the case of a male patient with SLE who presented with an exacerbation of bipolar disorder triggered by chloroquine. Firstly, when the patient was diagnosed with SLE, he underwent six months of therapy with chloroquine without any psychiatric symptoms. Later, the SLE returned and the patient was prescribed chloroquine again, without any mental illness. When the third exacerbation of SLE occurred, it coincided with a severe depressive episode with psychotic features that became aggravated for the first time after the administration of chloroquine. The chloroquine was subsequently replaced with hydroxychloroquine for the next six months without any behavioral problems, following which, the SLE and mood disorder were in remission. Later, a bipolar disorder relapse occurred, manifested by a manic episode, and in the following three months, despite psychiatric treatment, a manic episode with psychotic features developed four days after chloroquine was prescribed for arthritis. It was the second time that the mood disorder was exacerbated by chloroquine. Since that time, chloroquine has been withdrawn. Currently the patient is undergoing treatment with hydroxychloroquine and psychiatric drugs with good response. Our case points out that although chloroquine-induced psychosis is rare, patients presenting with behavioral changes need physicians' attention in order to diagnose early and efficiently treat encountered mood disorders.

Toll-like receptor 4 gene polymorphism 1196 C/T does not influence the risk of neuropsychiatric systemic lupus erythematosus in Polish population--a preliminary report.

OBJECTIVE: Recent data indicate that Toll-like receptors (TLRs) participate in various neuropathologic conditions, including ictogenesis, myelin disruptions associated with chronic alcohol abuse, behavioral and cognitive dysfunctions associated with alcohol-induced neuroinflammatory damage, and activation of microglia to reduce amyloid ß deposits. As seizures and depression are well known neuropsychiatric syndromes in systemic lupus erythematosus (SLE) the aim of the study was to investigate whether TLR4 gene polymorphism 1196C/T (rs4986791, Thr399Ile) was a candidate for susceptibility of development of neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: The study covered 60 patients with SLE and 100 healthy individuals. TLR4 1196C/T genotyping was performed by real-time polymerase chain reaction with the SimpleProbe. RESULTS: The SLE group comprised 86.7% of patients with wild-type homozygotes CC and 13.3% heterozygotes CT and no homozygotes TT. The control group consisted of 85% wild-type homozygotes CC, 15% heterozygotes CT and no homozygotes TT. The frequencies of genotype and allele distribution in SLE patients did not differ significantly from those of the control subjects. The probability of describing the possible risk of SLE imputed to genotype did not significantly differ in comparison with the healthy individuals (p = 0.77, odds ratio = 0.87, 95% confidence interval 0.34-2.19). A significant genotype association of genotype CC with arthritis was found in SLE patients (p = 0.02). It was further confirmed by a significant association of a dominant allele C with arthritis (p = 0.02). No association between CC and CT genotypes of TLR4 1196C/T and NPSLE was found. Allele distribution of TLR4 1196C/T also was not associated with NPSLE. No other significant differences were found in genotype and allele frequencies regarding clinical manifestation of SLE patients. CONCLUSION: In the Polish population of SLE patients, 1196C/T polymorphism of TLR4 gene does not increase the risk of development of NPSLE; however, genotype CC and a dominant allele C is associated with arthritis in the course of SLE.

The role of T-regulatory cells and Toll-like receptors 2 and 4 in atopic dermatitis.

Regulatory T cells (Tregs), toll-like receptors (TLRs) and interleukin-17 (IL-17) play important role in inflammatory diseases; however, their relevance in atopic dermatitis (AD) pathogenesis is not clear. The aim of study was to evaluate the number of circulating Tregs and peripheral blood mononuclear cells (PBMC) expressing TLR2 and TLR4 receptors in patients with AD. PBMC and CD4+/CD25(high) + Tregs were isolated from the whole blood of 32 AD patients and 36 healthy volunteers. Expression of CD4+CD25+, TLR2 and TLR4 receptors and IL 17+ was assessed with the flow cytometry. In the peripheral blood of AD patients, the percentage of Tregs was significantly higher when compared with the controls (P=0.0003). The number of TLR2+PBMC and TLR4+ PBMC in AD patients was significantly lower than in the controls (P=0.035; P=0.001, respectively). Also the percentages of Tregs with expression of both TLR2+ and TLR4+ in AD patients were significantly lower than in the control (3.85 versus 21.6, P<0.0001; 2.2 versus 17.6, P<0.0001, simultaneously). The percentage of CD4+/CD25high+/FOXP3+ Treg lymphocytes with expression of IL-17 was significantly higher in AD group than in healthy subjects (0.3% versus 0.06%; P=0.011). Distinct number of Tregs and various distribution of TLR2 and TLR4 expression on PBMC in AD patients suggest their contribution in the pathogenesis of AD.

Vitamin D status in systemic lupus erythematosus patients and its association with selected clinical and laboratory parameters.

OBJECTIVES: To identify relationships between vitamin D serum levels and the presence of autoantibodies directed against vitamin D and levels of interleukin(IL)-17 and IL-23 in patients with systemic lupus erythematosus (SLE). METHODS: The study included 49 patients with SLE. Serum concentrations of 25(OH)D(3) were measured with electrochemiluminescence immunoassay (ECLIA). Enzyme-linked immunosorbent assays (ELISA) were used to determine antibodies directed against 1,25(OH)(2)D(3) and levels of IL-17 and IL-23 in serum of SLE patients. In evaluation of vitamin D status, the control group consisted of 49 age and gender matched healthy individuals, whereas in assessment of anti-vitamin D antibodies the control group comprised 30 sera from blood donors. RESULTS: Serum concentration of 25(OH)D(3) in SLE patients during the warm season was 18.47 ± 9.14 ng/ml, which was significantly decreased as compared with that of the control group - 31.27 ± 12.65 ng/ml (p = 0.0005). During the cold season a trend toward lower concentration of 25(OH)D(3) in SLE patients was revealed; however, it did not reach statistical significance (11.71 ± 7.21 ng/ml vs. 16.01 ± 8.46 ng/ml; p = 0.054). Results within the recommended range for vitamin D (30-80 ng/ml; 70-200 nmol/l) were observed only in three patients. The 25(OH)D(3) concentration was decreased in SLE patients with renal disease or leucopenia as compared with the levels in patients who did not have either problem (p = 0.006 and p = 0.047, respectively). The cold season was found to be a risk factor for vitamin D deficiency (<20 ng/ml) (odds ratio = 9.25; p = 0.005). Autoantibodies directed against 1,25(OH)(2)D(3) were detected in three SLE patients. No significant difference in 25(OH)D(3) serum concentrations was found between SLE patients with and without these autoantibodies. No link was shown between the existence of autoantibodies against 1,25(OH)(2)D(3) and clinical or laboratory findings, including IL-17 and IL-23 levels. However, serum concentrations of IL-23 were lower in patients with vitamin D deficiency (p = 0.037). CONCLUSIONS: SLE patients, especially those with leucopenia or renal involvement, are at high risk of vitamin D deficiency and require vitamin D supplementation. Some SLE patient sera contained 1,25(OH)(2)D(3) antibodies, but these antibodies do not appear to affect vitamin D levels.

Combination therapy with adapalene-benzoyl peroxide and oral lymecycline in the treatment of moderate to severe acne vulgaris: a multicentre, randomized, double-blind controlled study.

BACKGROUND: Oral antibiotics in association with a topical retinoid with or without benzoyl peroxide (BPO) are the recommended first-line option in the treatment of moderate to severe acne vulgaris. OBJECTIVES: To evaluate the efficacy and safety of oral lymecycline 300 mg with adapalene 0·1%-BPO 2·5% (A/BPO) fixed-dose gel in comparison with oral lymecycline 300 mg with a vehicle gel in subjects with moderate to severe acne vulgaris. METHODS: A total of 378 subjects were randomized in a double-blind, controlled trial to receive once-daily lymecycline with either A/BPO or vehicle for 12 weeks. Evaluations included percentage changes from baseline in lesion counts, success rate (subjects 'clear' or 'almost clear'), skin tolerability, adverse events and patients' satisfaction. RESULTS: The median percentage reduction from baseline in total lesion counts at week 12 was significantly higher (P < 0·001) in the lymecycline with A/BPO group (-74·1%) than in the lymecycline with vehicle group (-56·8%). The success rate was significantly higher (47·6% vs. 33·7%, P = 0·002) in subjects treated with lymecycline and A/BPO. Both inflammatory and noninflammatory lesions were significantly reduced at week 12 (both P < 0·001) with a rapid onset of action from week 2 for noninflammatory lesions (P < 0·001) and week 4 for inflammatory lesions (P = 0·005). The A/BPO and lymecycline combination was well tolerated. The proportion of satisfied and very satisfied subjects was similar in both groups, but the number in the A/BPO group who were 'very satisfied' was significantly greater (P = 0·031). CONCLUSION: These results demonstrate the clinical benefit of combining A/BPO with lymecycline in the treatment of moderate to severe acne vulgaris.

Effect of chloroquine phosphate treatment on serum MMP-9 and TIMP-1 levels in patients with systemic lupus erythematosus.

Antimalarials are widely used for the treatment of systemic lupus erythematosus. However, their mechanisms of action have not been fully elucidated. Literature data indicate that matrix metalloproteinases may play a role in the immune response and tissue damage that occur in autoimmune skin diseases. The aim of this study was to determine the effect of 3 months of chloroquine treatment on serum levels of MMP-9 and TIMP-1 in patients with systemic lupus erythematosus. The study group consisted of 25 patients with systemic lupus erythematosus and 25 sex- and age-matched healthy volunteers. Before drug administration, serum levels of MMP-9 and TIMP-1 were determined by enzyme-linked immunosorbent assay. The same procedure was performed after chloroquine treatment. We found significantly higher median serum levels of MMP-9 in patients with systemic lupus erythematosus before therapy (57.20 ng/ml) when compared with controls (44.50 ng/ml) (p < 0.001). After chloroquine therapy the median MMP-9 serum level of systemic lupus erythematosus patients decreased significantly (43 ng/ml; p < 0.001). Before treatment the median TIMP-1 serum level in the patients with systemic lupus erythematosus was significantly higher than in the control group (500 vs. 200 ng/ml; p < 0.001), and after therapy it increased significantly (750 ng/ml TIMP-1; p < 0.001). The results suggest that chloroquine treatment may affect the matrix metalloproteinase network, and this effect may contribute to the immunoregulatory and anti-inflammatory properties of antimalarials.

The influence of treatment on quality of life in systemic lupus erythematosus patients.

OBJECTIVE: Systemic lupus erythematosus is an autoimmune disease with uncertain prognosis as to the course. The patients need pharmacotherapy all their life. The main aim of this study was to determinate the impact of therapeutic schedules on patients' quality of life. METHODS: The study was performed on 83 patients who were divided into five groups according to methods of treatment used. Quality of life was measured using MOS SF-36. RESULTS: Obtained results revealed that therapeutic schedules have the highest influence on patients' social functioning. The more medicaments the patients use, the lower their quality of life. CONCLUSIONS: The type of medicaments and therapeutic schemes adopted affect the patients' quality of life. Nevertheless, quality of life and the patients' attitude to it are very subjective and are also influenced by the clinical state of the patients as well as many other factors such as socioeconomic and demographic.

Suberythemal ultraviolet B radiation alters the expression of cell cycle-related proteins in the epidermis of human subjects without leading to photoprotection.

BACKGROUND: Deregulation of the cell cycle proteins is one of the critical factors leading to cutaneous carcinogenesis. OBJECTIVES: To monitor the expression of cell cycle proteins in the epidermis of subjects after repeated exposure to ultraviolet (UV) B radiation, and to test for the development of photoprotection by subsequent irradiation with a single erythemal UVB dose. METHODS: A total of 26 healthy volunteers were divided into four groups: group 1 (n = 9) were given whole-body UVB irradiation for 10 consecutive days with 0.7 minimal erythema dose (MED), group 2 (n = 9) were irradiated as in group 1 followed 24 h later by a single UVB dose of 3 MED on buttock skin, group 3 (n = 4) were irradiated with a UVB dose of 3 MED on buttock skin, and group 4 (n = 4) were not irradiated. Skin biopsies were collected 24 h after the final irradiation and stained for cyclins A, B1, D1, and p16, p18, p21, p27, p53, pRB, Bax and Bcl-2. RESULTS: The expression of cyclin D1, p18 and p21 was significantly higher in groups 1 and 2 compared with the nonirradiated group 4 controls and, in group 2, the expression of pRB, p53 and Bax was also increased. In group 3, only p53 and Bax proteins were significantly elevated compared with group 4. The expression of cyclin D1, p16, p18, p27, pRB and Bcl-2 was higher in group 2 compared with group 3. CONCLUSIONS: Suberythemal UVB radiation was sufficient to cause changes in the expression of several epidermal cell cycle proteins. When tested by irradiation with a single erythemal UVB dose following the repeated exposures, no photoprotection against the UV-induced alteration in cell cycle protein expression was apparent.

Systematic administration of chloroquine in discoid lupus erythematosus reduces skin lesions via inhibition of angiogenesis.

BACKGROUND: Discoid lupus erythematosus (DLE) is a chronic cutaneous form of lupus erythematosus, characterized by inflammation and scarring skin lesions, with lymphocyte infiltration and vasodilation. Antimalarial drugs have beneficial therapeutic effects in DLE, partially resulting from their immunomodulating and photoprotective properties. The possible influence of these drugs on angiogenesis has not been previously evaluated. AIMS: To investigate the impact of chloroquine (CQ) treatment on the expression of vascular endothelial growth factor (VEGF, a major regulator of angiogenesis) and CD34 (a transmembrane glycoprotein expressed on endothelial cells and involved in tethering lymphocytes) in patients with DLE. METHODS: A 3-mm skin biopsy was taken from typical skin lesions in 10 people with DLE. Another biopsy was taken from the same area after 3 months of treatment with CQ (250 mg/day). Skin sections were stained with monoclonal antibodies directed against VEGF and CD34. The intensity of epidermal VEGF expression, and the number and area of CD34-positive dermal blood vessels were assessed. RESULTS: CQ treatment induced a reduction in epidermal VEGF expression. It also resulted in a significant decrease in the median number of CD34+ dermal blood vessels (from 219 to 125 vessels per mm(2)). Furthermore the median vessel area was significantly lowered from 9.76 x 10(6) to 6.92 x 10(6) mm(2) per mm(2) of the dermis. CONCLUSIONS: These results indicate that one beneficial effect of CQ treatment in DLE may be due to its antiangiogenic properties.

Life satisfaction together with positive and negative aspects in Polish patients with systemic lupus erythematosus.

PURPOSE: To determinate satisfaction with life together with positive and negative emotions in SLE patients and correlate them with each other and with activity of the disease, duration of the disease and age of the patient. METHODS: The study was conducted on 83 SLE patients who fulfilled at least 4 out of 11 ACR criteria. Satisfaction with life was measured by the Satisfaction with Life Scale. Positive and negative aspects were assessed by the Positive and Negative Affects Schedule. Other data were collected from the patients at the same time. RESULTS: SLE patients presented reduced satisfaction with life. Duration of the disease, as well as age of the patients had an influence on it. Correlations between patients' quality of life emotions and life's satisfaction were present. CONCLUSIONS: SLE as a chronic, incurable and unpredictable disease has a great influence on patients' life. The awareness of this may lead to better compliance and to develop a new strategy of therapy.

The influence of antimalarial treatment on IL-1beta, IL-6 and TNF-alpha mRNA expression on UVB-irradiated skin in systemic lupus erythematosus.

BACKGROUND: There are very few data addressing the mechanisms of antimalarial treatment benefit locally within the skin of patients with lupus erythematosus, at the level of cytokine messenger RNA (mRNA) expression. OBJECTIVES: The aim of this study was to evaluate whether 3 months of monotherapy with chloroquine influences the mRNA skin expression of interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) in nonirradiated and locally ultraviolet B (UVB) irradiated nondiseased skin of patients with systemic lupus erythematosus (SLE). PATIENTS/METHODS: Skin biopsies were collected from 14 patients with SLE 24 h after irradiation at one site and from an adjacent unirradiated site, before and after 3 months of chloroquine treatment. Messenger RNA levels for IL-1beta, IL-6 and TNF-alpha were determined by relative quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: There were no significant differences in the levels of mRNA cytokine expressions in the unirradiated sites before and after 3 months of chloroquine administration. In the irradiated sites, the expression of all three cytokine mRNA levels was significantly higher than in the unirradiated group, approximately 24 h after irradiation, before chloroquine treatment. Significantly lower expression of IL-1beta, IL-6 and TNF-alpha mRNAs was noted in irradiated skin samples after 3 months of chloroquine treatment. CONCLUSIONS: These results demonstrate the local inhibitory effects of chloroquine on UVB-induced upregulation in the mRNA expression of proinflammatory cytokines in irradiated skin of SLE patients, and provide further insight into the apparent immunomodulatory, anti-inflammatory and photoprotective properties of chloroquine.

Quality of life and socioeconomic factors in Polish patients with systemic lupus erythematosus.

OBJECTIVE: To determinate health related quality of life (HRQoL) in SLE patients and correlate it with socioeconomic factors. METHODS: The study was conducted on 83 SLE patients who fulfilled at least 4 out of 11 ACR criteria. HRQoL was measured by SF-36. Socioeconomic data were collected from the patients at the time of filling-up SF-36 questionnaire. RESULTS: SLE patients presented decreased HRQoL. Duration of the disease, as well as age of the patients, had an influence on it. Patients who lived in the villages obtained lower results than those from the cities. More educated patients assessed their HRQoL as higher. Surprisingly, patients who described their social conditions as worse presented better quality of life. There was a statistically significant correlations between HRQoL and socioeconomic factors.

Serum levels of angiogenic cytokines in systemic lupus erythematosus and their correlation with disease activity.

We investigated the serum concentration of hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGF-beta1) using an enzyme-linked immunosorbent assay (ELISA) in a group of 60 patients with systemic lupus erythematosus (SLE), and 20 healthy controls. We also examined the possible association between the serum concentrations of these factors and certain clinical, laboratory parameters and SLE activity. HGF, VEGF and TGF-beta1 were detectable in all patients with SLE, and in all normal individuals. bFGF was measurable in 70% of the patients with SLE and in 65% of the healthy controls. The HGF level was higher in active SLE (median 1,019.5pg/ml) than in inactive SLE (median 787.8 pg/ml) (p < 0.005) or in the control group (median 847.0 pg/ml) (p < 0.009). The level of VEGF in active SLE was also higher (203.5 pg/ml) than in inactive disease (116.1 pg/ml) (p < 0.05) or in healthy persons (133.5 pg/ml) (p < 0.04). The levels of bFGF and TGF-beta1 were similar for both the active and inactive SLE, and the control group (p > 0.05). We found a significant, positive correlation between the levels of HGF and bFGF (r = 0.268, p < 0.04), HGF and TGF-beta1 (r = 0.365, p < 0.005) and HGF and VEGF (r = 0.327, p < 0.02) as well as VEGF and TGF-beta1 (r = 0.543, p < 0.001). We found a positive correlation between VEGF serum levels and platelet counts (r = 0.272, p < 0.04), and the TGF-beta1 concentration and platelet count (r = 0.313; p < 0.02). There was also a positive correlation between HGF serum concentration and the SLE activity score (r = 0.435, p < 0.001), as well as between the level of VEGF and SLE activity (r = 0.252, p = 0.05). In conclusion, serum levels of the angiogenic factors HGF and VEGF may be relevant in SLE pathogenesis. Their concentrations seem to be markers of SLE activity.

Circulating interleukin-6 type cytokines in patients with systemic lupus erythematosus.

We investigated the serum concentration of interleukin-6 (IL-6) and the IL-6 family of cytokines (leukemia inhibitory factor (LIF), oncostatin M (OSM) and ciliary neurotrophic factor (CNTF) using an enzyme-linked immunosorbent assay (ELISA) in 64 patients with systemic lupus erythematosus (SLE) and 15 healthy controls. We also examined a possible association between the serum levels of these proteins and SLE activity as well as correlations between the IL-6 concentration and the levels of LIF, OSM and CNTF. IL-6 was detectable in all 64 patients with SLE and normal individuals, and the level of this cytokine was significantly higher in patients than in the control group (p < 0.002 ). LIF, OSM and CNTF were detectable in 9 (14.1%), 6 (9.4%) and 51 (78%) patients, respectively, and undetectable in the majority of healthy individuals. We found positive correlation between the serum concentrations of IL-6, LIF, OSM and CNTF and SLE activity. IL-6 and OSM serum levels were also correlated but not IL-6 and LIF or CNTF. In conclusion, an increase in the serum levels of IL-6 and, to a lesser extent of LIF, OSM and CNTF concentrations may be useful markers for SLE activity.

Generalized lichen nitidus: a case report.

We report the case of a 6-year-old boy with disseminated papular lesions. Clinical and histopathologic examinations confirmed the diagnosis of lichen nitidus. There was no improvement during a three-year observation period, despite various methods of treatment. In the fourth year, we observed spontaneous resolution of the skin lesions after sun exposure in the summer.

Pemphigus foliaceus: an unusual clinical feature and case reports.

Two cases of pemphigus foliaceus in 70-year-old women have been presented. The initial clinical picture, as well as results of histopathologic examinations, suggested the diagnosis of eczema. Because the therapy was not successful and changes in the clinical picture were observed, repeated histopathologic and immunofluorescent examinations were carried out. Presence of immunologic findings characteristic for pemphigus foliaceus formed the basis for verification of the diagnosis and administration of an appropriate therapy.

[Lupus erythematosus in newborns]. / Toczen rumieniowaty noworodków.

Neonatal lupus erythematosus is an uncommon disease described mainly through case reports. In this paper the pathogenesis, epidemiology, skin and organ manifestations of the disease were presented. The necessity of co-operation between physicians of different specialisations in the prevention and treatment was underlined.