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Background Effectiveness of ultraviolet (UV)A1 in flares of atopic dermatitis (AD) is thought to influence the expression of cytokines involved in its pathogenesis. The aim of the study was to investigate whether mRNA expression of human β defensin-1 (hβD-1) correlates with that of interleukin (IL)-4, IL-10, and IL-31 in skin lesions in AD before and after UVA1 phototherapy, to determine whether UVA1 decreases the expression of the aforementioned mediators, and to confirm whether changes in mRNA expression correspond with the clinical efficacy of UVA1. Methods Twenty-five patients with AD underwent medium-dose UVA1 phototherapy. Before and after UVA1, biopsies from acute skin lesions were studied using reverse transcription and real-time polymerase chain reaction. Results Levels of mRNA hβD-1 correlated with those of IL-10 and IL-31, levels of IL-4 mRNA correlated with those of IL-10 and IL-31, and IL-10 expression correlated with that of IL-31, both before and after UVA1. Phototherapy with UVA1 improved SCORing of Atopic Dermatitis (SCORAD) values, decreased pruritus, and increased expression of IL-4. After UVA1, no difference was found in the mRNA expression of other molecules. The SCORAD index did not correlate with the expression of any examined mRNA either before or after UVA1. Conclusions hβD-1, IL-4, IL-10, and IL-31 are expressed in acute skin lesions in AD, and their levels correlate with each other. UVA1 improves SCORAD and pruritus and increases the expression of IL-4 without direct effect on other molecules.

Background Vascular endothelial growth factor (VEGF) was found increased in the stratum corneum of patients with atopic dermatitis (AD). However, its potential pathogenic role(s) in AD needs further clarification. Objective The aim of this study was to determine whether VEGF serum levels correlate with other selected cytokine levels and features of AD. Methods VEGF and other cytokine levels were measured in 83 patients with AD and in a control group and then correlated with clinical and laboratory parameters of AD. Results The mean serum concentrations of VEGF and tumor necrosis factor α were significantly higher in patients with AD than in the control group, whereas the mean interleukin eight serum level was lower. VEGF concentrations correlated with the severity of AD as expressed by SCORAD index and objective SCORAD. Conclusion VEGF could be regarded as a potentially important mediator in the pathogenesis of AD, as VEGF levels correlate somewhat with AD severity.

Background The mechanisms responsible for the efficacy of ultraviolet A1 (UVA1) in the treatment of atopic dermatitis (AD) are not fully understood. Objectives This study was designed to investigate mRNA expression of thymic stromal lymphopoietin (TSLP), thymus- and activation-regulated chemokine (TARC), interleukin-5 (IL-5), and IL-13 in AD before and after UVA1 therapy, to determine correlations among them, and to examine whether UVA1 influences their expression and whether it is associated with UVA1 efficacy. Methods Twenty-five patients with AD underwent medium-dose UVA1 phototherapy. Before and after UVA1, biopsies from acute skin lesions were studied using reverse transcription and real-time polymerase chain reaction. Results Levels of mRNA TSLP correlated with those of TARC, IL-5, and IL-13, and levels of TARC correlated with those of IL-5 and IL-13, both before and after UVA1. Expression of IL-5 correlated with that of IL-13 only before UVA1. SCORAD (SCORing of Atopic Dermatitis) indices correlated with levels of TARC and IL-5 before irradiation. After UVA1, no mRNA level correlated with the SCORAD index. Phototherapy with UVA1 improved SCORAD values (P < 0.001) and increased expression of TARC (P < 0.05) but did not affect mRNA expression of TSLP, IL-5, or IL-13. Conclusions Expression levels of the mediators TSLP, TARC, IL-5, and IL-13 in AD are interrelated. Phototherapy with UVA1 improves SCORAD indices and increases expression of TARC but has no direct effects on the expression of other molecules. It is likely that UVA1 also interferes with or acts via intermediators on the link between IL-5 and IL-13.

Summary 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

Objective: The aim of this study was to determine the characteristic factors for vascular development and maintenance levels as well as correlation between Tie-1 receptors, Tie-2 receptors and the corresponding ligands - angiopoietins - in systemic sclerosis (SSc) patients. Materials and Methods: Serum levels of Tie-1, Tie-2, Ang-1 and Ang-2 were measured in 25 SSc patients and healthy controls. Results: There was a statistically significant difference in serum Tie-1 (p = 0.009) and Ang-2 (p = 0.001) levels in SSc patients compared with healthy controls. Significant correlations between Tie-1 and Tie-2 (ρ = 0.70, p = 0.0001) and between Tie-1 and Ang-2 (ρ = -0.92, p = 0.002) were found in the SSc group. Serum levels of Tie-2 were positively associated with esophagus changes (U = 2.03, p = 0.041) and Ang-1 was negatively correlated with duration of Raynaud's phenomenon (ρ = -0.75, p = 0.00008). Conclusion: The increase in serum concentration of Tie-1 and Ang-2 in patients with SSc may confirm a molecular imbalance between receptor tyrosine kinases Tie and their ligands.

Sonic hedgehog (Shh) pathway impairment plays a key role in the pathogenesis of basal-cell carcinomas (BCC), the most frequent skin tumor among Caucasians. Shh, Smo, and Gli2 family proteins are necessary for adequate and controlled cell proliferation. The aim of this study was to evaluate Shh, Smo, and Smo expression in BCC skin biopsies taken from sun-exposed areas. 41 BCC skin biopsies and 22 healthy skin specimens (the control group) taken from the same areas served as material for the study. All specimens were immunohistochemically stained with monoclonal antibodies directed against the chosen proteins. Shh and Smo expression (cytoplasmic pattern) were recorded semiquantitatively using a four-grade score (0-3). Gli2 expression (nuclear pattern) was determined using an image analysis system (semiautomatic function). The immunoexpression of the Shh and Smo proteins significantly increased in the BCC group, as compared with the normal controls (for Shh, the mean intensity was 1.67 in BCC vs. 1.17 in the control group, p < 0.001; for Smo, the mean intensity was 1.46 in BCC vs. 0.99 in the control group, p < 0.001). The staining for Gli2 in the BCC group was completely negative, but indicated the presence of Gli2 in the control patients (1.15 Gli2+ cells/100 cells). Sonic hedgehog pathway dysregulation may play an important role in skin cancerogenesis leading to BCC development.

Photosensitivity is an important and distinguishing sign in various subtypes of cutaneous lupus erythematosus (CLE); however, it remains poorly defined. The purpose of this study was to evaluate whether standardized photoprovocation is a reproducible method to assess photosensitivity in subjects with CLE. A total of 47 subjects with CLE (subacute cutaneous lupus erythematosus (SCLE), n=14; discoid lupus erythematosus (DLE), n=20; lupus erythematosus tumidus (LET), n=13) and 13 healthy volunteers underwent photoprovocation at seven European sites. Of these, 22 (47%) subjects (57% SCLE, 35% DLE, and 54% LET) and none of the healthy volunteers developed photoprovoked lesions according to clinical analysis. Of these 22 subjects, 19 (86%) developed lesions that were histopathologically confirmed as specific for lupus erythematosus (LE). In CLE subjects who developed UV-induced lesions, 86% had Fitzpatrick's phototypes I or II, and the mean minimal erythema dose (MED) was significantly lower compared with subjects without UV-induced lesions (P=0.004). No significant differences in photoprovocation results were observed between study sites. Safety parameters showed no clinically meaningful differences between CLE subjects and healthy volunteers after photoprovocation. In conclusion, a standardized, safe, and reproducible protocol for photoprovocation using UVA and UVB radiation induced skin lesions in approximately half of all CLE subjects and showed comparable results across multiple sites. This method may therefore be used for future diagnostic testing and clinical trials.

To assess the correlation between quality of life (QoL) and satisfaction with life (SL) in SLE patients and correlate both with clinical symptoms of the disease. The study was performed in 83 patients. QoL was assessed by Short Form 36, and SL was assessed by the Satisfaction with Life Scale. Clinical manifestations presented at the time of examination were taken into consideration. SLE patients assessed their QoL and SL as rather low. Those with photosensitivity as well as neurological symptoms presented lower QoL in particular domains, while those with renal manifestation of SLE assessed their QoL as higher. Similar observations were made for SL only in relation to neurological symptoms. Moreover, our findings show that although SL is a part of QoL, both these parameters should be distinguished in order to fully assess the state of the patient.

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.

Hailey-Hailey disease, or familial benign chronic pemphigus, is an autosomal dominant genodermatosis. Disease symptoms may contribute to an adverse impact on quality of life and functional limitation and disability. As Hailey-Hailey disease is chronic and frequently recalcitrant to treatment, multiple therapeutic approaches, including surgical options, have been attempted. We describe here three cases of recalcitrant Hailey-Hailey disease that showed long-term improvement with radiotherapy. Axillary lesions were treated with electron beam at an anti-inflammatory dose (energy 6-8 MeV). Patients received 20 Gy in 10 fractions to 90% isodose, at each axilla. No disease recurrence was observed during a 38 months follow-up of the treated sites. The effect of radiotherapy was thus considered to be locally beneficial, but without any positive influence on the general course of the disease.

Summary 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 mm2). Furthermore the median vessel area was significantly lowered from 9.76 × 106 to 6.92 × 106 mm2 per mm2 of the dermis. Conclusions. These results indicate that one beneficial effect of CQ treatment in DLE may be due to its antiangiogenic properties.

Ultraviolet radiation suppresses contact hypersensitivity (CHS). The role of epidermal Langerhans cells (LCs, CD1a(+)) in the elicitation phase of CHS is uncertain. To assess the effect of low-doses of solar simulated radiation (SSR) on LC numbers at the CHS elicitation site. 3 groups (each about 30 volunteers) were whole-body irradiated with suberythemal SSR on 2, 10 or 30 consecutive days before sensitization with diphenylcyclopropenone. Another group was not irradiated. Elicitation of CHS took place 3 weeks later with subsequent evaluation by visual scoring and spongiosis grade. CD1a(+) cells in the epidermis from the elicitation site were counted. No difference in CHS intensity between the unirradiated controls and all 3 irradiated groups was found, but a significant negative correlation between the spongiosis grade and the number of SSR exposures was shown. The number of epidermal CD1a(+) cells in the 10- and 30-day groups was reduced compared with the unirradiated group, and the 30-day group had significantly fewer than the 10-day group. Low daily doses of SSR induce suppression of CHS, leading to depletion of LCs at the CHS elicitation site. The effect on the CHS and LCs is cumulative, indicating that photoadaptation for these parameters does not develop over the 30 day irradiation period.

The impact of repeated doses of solar simulated radiation (SSR) has not been evaluated, particularly to determine if photoadaptation and photoprotection develop over time. In this study, erythema, pigmentation, cyclooxygenase (COX)-1 and 2 expression and thymine dimer (dTT) formation were evaluated in the skin of irradiated subjects of phototype II or III. Groups of 7-10 volunteers were whole-body irradiated with a low dose of SSR on each of 10 consecutive days followed by a single erythemal ultraviolet B (UVB) dose on a small body area, or irradiated only with the single erythemal UVB dose on a small body area, or irradiated with the low dose of SSR on each of 30 consecutive days, or were unirradiated. Erythema and pigmentation were measured 24 h after the final SSR or UVB, and skin biopsies collected for the assessment of COX(+) cells and dTT(+) nuclei. The repeated SSR exposures induced a small increase in pigmentation without erythema, and were slightly protective against the erythemal effects of the subsequent high UVB dose. The number of COX-1(+) and 2(+) cells increased as a result of 10-days SSR and rose still further after 30-days SSR, indicating that photoadaptation had not developed. The SSR exposures did not result in any protection against the further increase in COX-1 and 2 expression caused by the erythemal UVB dose. In contrast, for dTT formation, the repeated SSR exposures led to a limited degree of both photoadaptation and photoprotection.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can be exacerbated by exposure to ultraviolet radiation (UVR). The number and phenotype of antigen presenting cells in the skin play a role in cutaneous immune response generation. Although antimalarials are widely used in SLE treatment, their mode of action is not completely elucidated. The aim of our study was to determine the effect of chloroquine treatment on HLA-DR+ and CD1a+ cell number in locally irradiated (three minimal erythema doses of UVB) and normal appearing skin in SLE patients and healthy subjects. A significantly higher number of HLA-DR+ and CD1a+ cells were found in both locations in SLE patients compared with controls. Following three months of daily chloroquine treatment (250 mg), the HLA-DR+ and CD1a+ cell counts were significantly reduced in both irradiated and unirradiated sites of SLE patients, although still higher than in controls. Chloroquine treatment reduces the number of antigen presenting cells in the skin of SLE patients, and this effect may explain the antimalarials beneficial immunoregulatory and anti-inflammatory properties.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a complex pathogenesis. Published data have revealed that serum levels of proinflammatory cytokines are increased in SLE patients.The aim of our study was to evaluate whether monotherapy with chloroquine phosphate affects IL- 1β, IL-6, IL-18 and TNF-α serum levels in SLE patients. The study group consisted of 25 SLE patients with mild or moderate disease activity and 25 age- and sex-matched healthy control subjects. In SLE patients the cytokine levels were measured just before and three months after starting chloroquine treatment at a dose of 125 mg twice daily.Although the majority of SLE patients had a low systemic lupus activity measure (SLAM) index, the levels of IL-6, IL-18 and TNF-α were significantly higher than in the control group. After three-months of chloroquine therapy the mean level of IL-6, IL-18 and TNF-α decreased significantly. Minimal erythema doses (MEDs) were significantly increased in SLE patients after three months of chloroquine therapy.The results indicate that chloroquine treatment lowers some proinflammatory cytokines and may provide a photoprotective effect.

We investigated in vivo the relationship between the degree of peripheral blood lymphocyte apoptosis and circulating dendritic cells (DC) as well as the immunological status in 45 patients with systemic lupus erythematous (SLE). Apoptosis was detected by phosphatidylserine externalization and assays to detect caspase activation. The total DC count (tDC) and their myeloid, mDC1 (BDCA1+) and mDC2 (BDCA3+), and plasmacytoid, pDC (BDCA3+), subtypes were assessed. Moreover, several immunological parameters, such as complement proteins, interferons (IFN), tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, and IL-6 levels were assessed. There were no significant differences in both the intensity of apoptosis and DC counts between active and inactive SLE as well as between untreated patients and those treated with steroids. The incidence of lymphocyte apoptosis correlated positively with T-cell count, both T-helper (p=0.004) and cytotoxic T cells (p=0.001), but not with B or natural killer (NK) cells. The intensity of apoptosis enhanced along with the increase in complement C3 (p=0.016) and decrease in IFN-gamma (p=0.040) levels. The apoptotic cell count correlated with tDC (p=0.031), mDC1 (p=0.007), and pDC (p=0.039) counts. Both tDC and mDC1 counts correlated positively with antinuclear antibody (ANA) titers (p=0.017 and 0.032, respectively). Moreover, tDC correlated with C4 (p=0.039) and pDC with both C3 (p=0.032) and C4 (p=0.007) levels. The DC counts correlated inversely with IFN-gamma (tDC, p=0.038; mDC1, p=0.009), IL-6 (mDC2, p=0.031), or serum IgG levels (tDC, p=0.006; mDC1, p0.001; mDC2, p=0.001). We found a positive correlation between lymphocyte apoptosis and peripheral blood DC count as well as the level of complement proteins in patients with SLE. The enhanced lymphocyte apoptosis was accompanied by the decrease in concentration of some cytokines, such as IFN-gamma or IL-6, as well as serum IgG level. This finding may reflect pathogenetic events during development of the disease, which include a persistent signal derived from circulating apoptotic lymphocytes, mobilizing the complement system, and attracting peripheral blood DC.

Rosacea is a chronic facial dermatosis with a progressive course, which is characterized by the presence of erythema, papules, pustules, telangiectasias and sebaceous gland hyperplasia. However, the aetiology is still unknown; genetic predisposition, gastrointestinal disorders (Helicobacter pylori), infestations with Demodex folliculorum and environmental stimuli are considered to be involved in the inflammatory process. A metabolite of nicotinamide, 1-methylnicotinamide (MNA(+)), has anti-inflammatory properties, and this is the first study to test the effectiveness of this agent in treating rosacea. In total, 34 patients with rosacea were treated with a gel containing 0.25% MNA(+) as a chloride salt, twice daily for 4 weeks, after which improvement was observed in 26/34 cases. The improvement was good in 9/34 and moderate in 17/34, but no clinical effect was noted in seven subjects. In only one case was skin irritation given as the reason for treatment withdrawal. These results indicate that MNA(+) might be a useful agent for treating rosacea.

Fibrosis of oesophagus, lungs, heart, and kidney in the course of systemic sclerosis (SSc) may lead to dysfunction of the above organs or even patients death. Recent studies point out the role of angiogenesis and fibrosis disturbances in the pathogenesis of SSc. Heart fibrosis is one of the most important prognostic factors in SSc patients. So, the aim of our study was to examine cardiovascular dysfunction in SSc patients and its correlation with serum levels of vascular endothelial growth factor (VEGF), endostatin, and tissue inhibitor of metalloproteinase 2 (TIMP2). The study group comprised 34 patients (19 with limited scleroderma (lSSc) and 15 with diffuse scleroderma (dSSc)). The control group consisted of 20 healthy persons, age and sex matched. Internal organ involvement was assessed on the basis of specialist procedures. Serum VEGF, endostatin, and TIMP2 levels were evaluated by ELISA. We found cardiovascular changes in 15 patients with SSc (8 with lSSc and 7 with dSSc). The observed symptoms were of different characters and also coexisted with each other. Higher endostatin serum levels in all systemic sclerosis patients in comparison to the control group were demonstrated (P<.05). Also higher serum levels of endostatin and TIMP2 were observed in patients with cardiovascular changes in comparison to the patients without such changes (P<.05). The obtained results support the notion that angiogenesis and fibrosis disturbances may play an important role in SSc. Evaluation of endostatin and TIMP2 serum levels seems to be one of the noninvasive, helpful examinations of heart involvement in the course of systemic sclerosis.

Dermatitis herpetiformis (DH) is a subepidermal autoimmune disease characterized by skin and intestinal lesions consistent with coeliac disease. There are also some data that metalloproteinases (MMPs) are involved in the development of skin lesions in DH, however their exact role in this process is not fully understood. The aim of the study was to investigate whether MMPs and their inhibitors are involved in pathogenesis of DH. Skin biopsies were taken from 13 patients with active DH and from 10 healthy subjects. The localization and expression of MMPs and TIMPs were examined by immunohistochemistry. MMPs expression was detected in basal keratinocytes and in the whole epidermis in all of the DH subjects. Neutrophils in microabscesses and in blister fluid were also positive for MMPs. Expression of TIMPs was moderate or weak in all examined biopsies. Our results allow us to conclude that imbalance between these enzymes takes an important role in the pathogenesis of DH.

SUMMARY Varicella zoster virus (VZV) causes varicella (chickenpox) as the primary infection and zoster (shingles) on reactivation from latency, often many years later. One of the most common and most severe sequela of zoster is postherpetic neuralgia (PHN). Apart from age, factors which predispose towards PHN are unknown. In the present study, the concentration of a variety of Th1 and Th2 cytokines in the serum of 30 zoster patients at the time of the acute disease were correlated with the subsequent development of PHN in nine of these patients, but no association was found. In addition, although some cytokines such as IFN-γ, IL-6 and IL-8 were slightly raised in the zoster group compared with a group of normal healthy subjects of a similar age distribution, these differences only verged on significance. Antibody titres to VZV were raised in the zoster group compared with the controls but these did not differ between the patients who developed PHN and those who did not. Biopsies of zoster lesions were collected from nine patients. There were significantly fewer infiltrating lymphocytes in the lesions of the three patients who subsequently developed PHN compared with the six who did not, although the expression of the neuropeptide, substance P, did not differ between the two groups. It is possible that the poor inflammatory response at the time of the acute zoster may result in less effective containment of the VZV and more damage in the dermatome, thus contributing to the persistence of the neuralgia.

Background: Nodular amyloidosis is a rare form of localized cutaneous amyloidosis that is characterized by nodules located on the extremities, trunk, genitalia, or face. In treatment regimens, many approaches have been described, including carbon dioxide (CO2) laser therapy. Objective: We present a case of a 60-year-old white male with a 20-year history of disseminated waxy, purpuric, yellowish, and bullous skin lesions on the trunk and extremities. The skin changes were accompanied by pain during palpation and were temporarily pruritic. Method: Based on histologic and direct immunofluorescence test findings, the diagnosis of cutaneous nodular amyloidosis was established. Skin lesions were treated with a CO2 laser. During surgery, treated tissue was found to be slightly friable, and there was a little problem with hemostasis that correlated with amyloid infiltration of the dermis and blood vessels. However, after 8 weeks, we observed clinical improvement of all treated areas with the presence of atrophic scars. In the regions of laser therapy, no recurrence of the disease was observed during a 12-month follow-up. Conclusion: Based on these results, we conclude that CO2 laser has a beneficial effect in the treatment of nodular amyloidosis; however, surgery procedures may be associated sometimes with tissue friability and poor hemostasis. Contexte: L'amylose nodulaire est une forme rare d'amylose cutanée localisée, qui se caractérise par des nodules situés sur les membres, le tronc, les organes génitaux, et la face. Diverses formes de traitement ont été décrites, notamment le traitement au laser à gaz carbonique (CO2). Objectif: Nous exposons ici le cas d'un homme de 60 ans, de race blanche, présentant, depuis une vingtaine d'années, des lésions cutanées bulleuses, jaunâtres, purpuriques, et d'apparence cireuse, disséminées sur le tronc et les membres. Les lésions s'accompagnaient de douleur à la palpation et étaient prurigineuses pendant un certain temps. Méthode: Le diagnostic d'amylose nodulaire cutanée a été posé d'après les résultats de l'examen histologique et de l'immunofluorescence directe. Les lésions ont été traitées au laser à CO2. Les tissus se montraient légèrement friables durant la chirurgie, et l'hémostase était quelque peu difficile en raison de l'infiltration amyloïde du derme et des vaisseaux sanguins. Toutefois, une amélioration clinique de toutes les régions traitées a été marquée, au bout de 8 semaines, par l'apparition de cicatrices atrophiques. Il n'y a pas eu de récidive de la maladie dans les régions traitées au laser, au cours d'un suivi de 12 mois. Conclusion: Nous avons déduit des résultats que le laser à CO2 avait un effet favorable sur l'amylose nodulaire; cependant, l'intervention chirurgicale peut parfois être gênée par la friabilité des tissus et une mauvaise hémostase.

Serum concentrations of three angiogenic cytokines: vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukin-18 (IL-18) and antiangiogenic factor endostatin in the serum of 52 patients with systemic lupus erythematosus (SLE) and 20 healthy subjects were investigated. The possible association between serum levels of these proteins and SLE activity as well as correlation between the concentrations of angiogenic cytokines and the level of endostatin was also analyzed. VEGF and IL-18 were detectable in all SLE patients and healthy control group. bFGF was measurable in 71.2% of patients with SLE and 65% of healthy persons. Endostatin was detectable in 94.2% of SLE patients and 95% of normal subjects. The serum levels of endostatin and bFGF were not significantly different in SLE and healthy control (P > 0.05). The median concentration of VEGF was higher in active SLE (238.4pg/ml) than in inactive disease (118.1pg/ml, P < 0.05) or in control group (133.5pg/ml, P < 0.04). The median serum level of IL-18 was higher in the SLE patients (595.2pg/ml) than in the control group (252.7pg/ml) (P < 0.001). The correlations between the levels of angiogenic cytokines and endostatin with clinical features, laboratory abnormalities and also with the type of treatment were analysed. We found a positive correlation between VEGF serum concentration and SLE activity according to SLAM score (r=0.275, P < 0.05). The significant positive correlation was also found between IL-18 and endostatin (r=0.289, P < 0.04). In contrast, the correlation between bFGF and endostatin was significantly negative (r=7 0.299, P < 0.04). In conclusion, serum levels of the angiogenic and antiangiogenic factors may play an important role in SLE pathogenesis.

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.

Systemic lupus erythematosus (SLE) is a disorder with a wide range of immunological abnormalities. The results of the studies undertaken in the last decade indicated that SLE pathogenesis was mainly connected with the breakdown of the activation control of B and T cells, generating humoral or cell-mediated responses against several self-antigens of affected cells. The last studies demonstrate that the role of γδ T lymphocytes in autoimmune diseases can be especially important. Flow cytometry techniques were used to investigate the number and percentage of TCR γδ T cells and their most frequent subtypes in peripheral blood of 32 patients with SLE and 16 healthy volunteers. We also correlated TCR γδ cells number with the level of T CD3+, T CD4+, T CD8+, and NK (CD16) cells (cytometric measurements) and SLE activity (on the basis of clinical investigations). Our studies were preliminary attempts to evaluate the role of that minor T cell subpopulation in SLE. Absolute numbers of cells expressing γδ TCR in most SLE blood specimens were significantly lower than in the control group (P<0.006). However, since the level of total T cell population was also decreased in the case of SLE, the mean values of the percentage γδ T cells of pan T lymphocytes were almost the same in both analysed populations (7.1% vs 6.3%, respectively). In contrast to Vδ2+ and Vγ9+ subtypes of pan γδ T cells, Vδ3+ T cells number was higher in SLE patients (20×10 cells/μl) than in healthy control group (2×2 cells/μl) (P=0.001). However, we found no differences between the numbers of pan γδ T lymphocytes and studied their subtypes in the patients with active and inactive disease. These cell subpopulations were doubled in the treated patients with immunosuppressive agents in comparison with untreated ones; however, data were not statistically significant. Our study indicated that Vδ3+ subtype of γδ T cells seems to be involved in SLE pathogenesis; however, we accept the idea that the autoimmunity does not develop from a single abnormality, but rather from a number of different events.

We estimated the serum levels of IL-6, TNF-α and IL10, and generation of superoxide radicals, as well as their mutual dependence, in 63 SLE patients at various stages of disease activity. Our results indicate a statistically significant increase of the serum levels studied, and an increase of superoxide anion generation by granulocytes, in correlation with SLE activity. These results indicate that oxygen metabolism and the examined cytokines play an important role in pathogenesis of SLE. The assessment of these parameters can be useful in the estimation of disease activity.

A 45-year-old man presented with a 7-year history of keratosis lichenoides chronica (KLC), a mucocutaneous lichenoid disorder of keratinization with no known aetiology, without significant systemic associations. Our patient also had type I diabetes mellitus, mild hypertension and lipid abnormalities. The diagnosis and treatment of KLC is often challenging.

Systemic lupus erythematosus (SLE) is an autoimmune disease of multifactorial pathoaetiology. Different organs and blood vessels may be affected by chronic inflammation. A direct cause of the disease has not yet been found, so research is being carried out to this effect. The role of the recently identified helper T lymphocyte CD4+, described as Th17, and its dependent cytokines have been of particular interest. The aim of the study was to evaluate IL-17A, IL-17B, IL-17F and IL-23 in 60 SLE patients and 26 age-matched, healthy volunteers and also to investigate the correlation between levels of the investigated cytokines and VEGF, PIGF, as well as number of endothelial cells. IL-17A, IL-17B, IL-17BR and IL-17F levels were found to be higher in SLE patients than in the control group. However, only IL-17F levels showed a statistically significant correlation with the number of endothelial cells (aCEC) and disease activity. Correlations between levels of IL-17F and VEGF and PIGF as well as VEGF and IL-17A and IL-23 were statistically significant. Increased levels of the selected cytokines from the IL-17 family in SLE patients suggest a role for them not only in the inflammatory process but also in angiogenesis. This also highlights the role of IL-17F in activating vascular endothelial cells and consequently blood vessel formation, and in the relationship between the inflammatory reaction and angiogenesis in the development of SLE.

Scientific communications indicate the disturbed expression of neuropeptides in the skin and serum in psoriasis vulgaris (PsV) patients. Narrow-band ultraviolet radiation (NB-UVB) is one of the systemic therapies of PsV. The aim of the study was to evaluate the influence of NB-UVB therapy on substance P (SP), calcitonin gene-related peptide (CGRP), brain-derived neurotrophic factor (BDNF), corticotropin-releasing factor (CRF) and interleukin-31 (IL-31) serum concentrations in PsV patients. 59 psoriatic patients with mean PASI (psoriasis area and severity index) 14.3 were treated with NB-UVB (20 exposures). The control group consisted of 50 healthy subjects, whose age and sex matched. In all patients, serum concentration of BDNF, CRF, IL-31 substance P and CGRP was analyzed by ELISA before the treatment and in psoriatic group the analysis was also done after 10 and 20 irradiations. In patients there was found a significantly higher concentration of IL-31 (215.3 vs. 748.6 ng/ml; p

Background Because vitamin D has immunomodulatory properties and immunologic mechanisms play a role in the pathogenesis of atopic dermatitis (AD), it is possible that vitamin D may influence the activity of AD. Objective The aim of the study was to correlate vitamin D concentrations in patients who had AD with clinical, immunologic, constitutional, and environmental factors, and to determine if vitamin D supplementation affects the clinical manifestations of AD. Methods Clinical and laboratory parameters of 95 patients with AD and 58 control subjects were measured. Severity of AD was assessed with the SCORAD index. Results The mean serum concentration of 25(OH)D 3 in patients with AD was not statistically different from control subjects. The frequency of bacterial skin infections was higher in patients with AD who had lower 25(OH)D 3 levels. No statistical associations between vitamin D levels and other multiple laboratory and clinical parameters were found. After supplementation both mean objective SCORAD and SCORAD index were significantly lower ( P Limitations All study patients were Caucasians and only one supplemental vitamin D dose and treatment duration were assessed. Conclusion The results from this study indicate that vitamin D supplementation may help ameliorate clinical signs of the disease and can be considered as a safe and well-tolerated form of therapy.

Background: Pemphigus is an autoimmune blistering disease mediated by circulating IgG autoantibodies directed against desmogleins 3 and/or 1. As pemphigus is a T cell–mediated disease, one may assume that genetically determined disregulation of costimulatory signal may be involved in its pathogenesis. Objective: The aim of the present study was to evaluate the relationship between polymorphisms in genes encoding costimulatory receptors, CTLA4 and ICOS, and pemphigus in the Polish population. Methods: The study included 54 patients with pemphigus: 40 with pemphigus vulgaris (PV) and 14 with pemphigus foliaceus (PF). Additionally, 176 healthy unrelated blood donors served as controls. +49A/G CTLA4 and IVS1+173 ICOS polymorphisms were identified using a modified polymerase chain reaction–restriction fragment-length polymorphism. Results: Analysis of the frequency of genotypes and alleles of +49A/G CTLA4 gene polymorphism showed no statistically significant differences between the PV and PF patients and the controls. The distribution of genotypes in IVS1+173 ICOS polymorphisms was significantly different in both PV ( p < .01) and PF ( p = .0004) patients when compared to controls. The carriers of the allele C were more frequent in PV or PF in comparison with the control group ( p < .001 for both groups). Conclusions: Our results suggest that genetically determined abnormal function of costimulatory receptors in T cells may be associated with the pathogenesis of pemphigus.

DENDRITIC cells are a complex group of mainly bone-marrow-derived leukocytes that play a role in autoimmune diseases. The total number of circulating dendritic cells (tDC), and their plasmacytoid dendritic cell (pDC) and myeloid dendritic cell (mDC1 and mDC2) subpopulations were assessed using flow cytometry. The number of tDC and their subsets were significantly lower in systemic lupus erythematosus patients than in the control group. The count of tDC and their subsets correlated with the number of T cells. The number of tDC and pDC subpopulation were lower in the patients with lymphopenia and leucopoenia than in the patients without these symptoms. Our data suggest that fluctuations in blood dendritic cell count in systemic lupus erythematosus patients are much more significant in pDC than in mDC, what may be caused by their migration to the sites of inflammation including skin lesions. Positive correlation between dendritic cell number and TCD4+, TCD8+ and CD19+ B cells, testify of their interactions and influence on SLE pathogenesis. The association between dendritic cell number and clinical features seems to be less clear.

Summary 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.

The aim of our study was to assess absolute counts of different subpopulations of circulating endothelial cells (CEC) in patients with active and inactive systemic lupus erythematosus (SLE). We have also investigated a potential correlation of CEC numbers with serum levels of angiogenic proteins as well as with clinical and laboratory symptoms of the disease. For the first time in SLE, CEC were enumerated directly, by the 'single platform' method. Resting (rCEC), activated (aCEC) and progenitor (pCEC) endothelial cells were identified in patients with SLE and healthy volunteers using four-colour flow cytometry. Serum concentrations of angiogenic proteins (vascular endothelial growth factor, placental growth factor (PIGF), soluble vascular cell adhesion molecule and endoglin) were evaluated by ELISA. The SLE activity was scored according to the Systemic Lupus Activity Measure system. We found that total CEC number in patients with SLE was significantly higher (median 14.2/microL) than in the control group (median 3.3/microL) (P < 0.0001). Absolute counts of aCEC, rCEC and pCEC (medians 4.9/microL, 6.8/microL and 2.3/microL, respectively) were also higher in patients with SLE than in healthy persons (medians 0.9/microL, 1.6/microL and 0.1/microL, respectively), with P < 0.0001 for all comparisons. There was no correlation between CEC or their subpopulations and SLE activity. Strong positive correlations were found between CEC, rCEC and pCEC numbers and serum levels of PIGF. Moreover, aCEC, rCEC and pCEC counts were significantly higher in SLE patients with leukopenia. In conclusion, our results show that absolute CEC counts and angiogenic proteins levels are elevated in patients with SLE as compared with healthy controls. These data may suggest that angiogenic process is involved in the pathogenesis of this disease.

Objective To investigate whether repeated exposures to low-dose UV or solar-simulated radiation induce apoptosis of peripheral blood mononuclear cells. Design Cohort study in a healthy population. Setting Departments of Dermatology and Hematology, Medical University of Lodz, Lodz, Poland. Participants Ninety-eight healthy volunteers were divided into the following 4 groups: group A, whole-body irradiated with a 0.7–minimal erythema dose (MED) of UV-B daily on 10 consecutive days followed by a single dose of 3 MEDs on a small body area 24 hours later; group B, whole body irradiated with 120 J/m 2 solar-simulated radiation (10 consecutive days, then single-dose UV-B exposure of 3 MEDs on a small body area after 24 hours); group C, irradiated with a single UV-B dose of 3 MEDs on a small body area; and group D, irradiated with a single UV-B dose of 4 MEDs on a small body area. Main Outcome Measure Apoptosis of peripheral blood mononuclear cells as well as expression of several apoptosis-regulating proteins in response to irradiation. Results Ten daily whole-body suberythemal exposures to UV-B or solar-simulated radiation enhanced the apoptosis of peripheral blood mononuclear cells, while the single erythemal doses on the small body area, either on their own or following the repeated exposures, did not increase the level significantly. Increase in Bax and p73 protein expression and down-regulation of Mcl-1 and Bcl-2 correlated with enhanced apoptosis. Conclusion Repeated suberythemal UV exposures enhance the apoptosis of peripheral blood mononuclear cells in healthy subjects.

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. Conflicts of interest None declared

Summary 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)-1β, IL-6 and tumour necrosis factor-α (TNF-α) 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-1β, IL-6 and TNF-α 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-1β, IL-6 and TNF-α 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.

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.

Pemphigus is a severe autoimmune disease characterized by circulating and bound in vivo pemphigus autoantibodies. It was revealed that the autoantibodies occur in healthy first-degree relatives of pemphigus patients; however, their significance is not fully elucidated. Thus, the aim of the study was to assess the frequency of circulating IgG pemphigus autoantibodies in the healthy relatives of pemphigus patients and of their ability to bind in vivo in the epidermis. We also analyzed IgG subclasses distribution, both in the serum-positive relatives and in the patients. Our study included 67 healthy relatives, 50 healthy normal controls and 33 patients (25 at an active stage of the disease, 8 in clinical remission). To detect circulating pemphigus antibodies we applied indirect immunofluorescence and anti-desmoglein ELISA. Monoclonal anti-human IgG1, IgG2, IgG3, IgG4 antibodies were used to assess subclass distribution. The frequency of circulating pemphigus autoantibodies in the relatives, detected by IIF (30/67) was statistically higher (P

Background The accurate incidence of delusional parasitosis (DP) is difficult to assess. The aim of this study was to analyse the frequency of DP treated by dermatologists, and to evaluate the treatment modalities they applied. Material and methods A specially designed questionnaire was distributed to 172 dermatologists. A total of 118 doctors responded (68.6% of all subjects). The dermatologists were asked to answer questions concerning demographic data of the respondents and the frequency of DP observed in their everyday practice. Finally, methods of treatment used by the dermatologists to help patients suffering from DP were evaluated. Results During the whole working period the majority of dermatologists participating in the survey (84.7%) had seen at least one patient with DP in their practice. About one-third of the respondents (33%) had seen one or two cases of DP during the past 5 years, and 28% of the doctors treated from three to five such patients. Twenty-three per cent of dermatologists declared that they had diagnosed no cases of DP during the past 5 years. The rest of our respondents had seen more than five cases of DP during the past 5 years, and 7% of the doctors reported seeing more than 10 patients with DP within this period. Almost 20% of the dermatologists were currently treating a patient with DP. Our data show that 40.7% of the respondents always ask and 28.8% often ask for a psychiatric opinion about their patients with DP. More experienced dermatologists statistically more frequently (P

Summary Background Exposure of human subjects to ultraviolet (UV) B radiation causes immunosuppression. Most experiments to date have not tested the effects of low daily doses of UVB radiation. Objectives To ascertain whether photoprotection against several UV-induced immune effects might develop following repeated exposure. Methods Groups of approximately 30 healthy individuals were given whole-body UVB irradiation on each of 10 consecutive days with 0.7 minimal erythema dose, or whole-body irradiation as before followed by a single erythemal UVB dose on a small body area, or irradiated only with a single erythemal UVB dose on a small body area, or were not irradiated. They were sensitized with diphenylcyclopropenone (DPCP) 24 h after the final dose, and skin biopsies collected to assess cytokine mRNA expression and the number of cells with thymine dimers and expression cyclooxygenase (COX)-1 and COX-2. Results The contact hypersensitivity (CHS) response to DPCP was significantly lower in the three irradiated groups compared with the unirradiated controls, while cutaneous interleukin (IL)-1β, IL-6, IL-10 and tumour necrosis factor-α mRNAs, COX-1 and COX-2 and thymine dimers were all significantly higher. When the single erythemal UVB dose was given following the repeated low exposures, a slight downregulation in cytokine expression and thymine dimer formation was indicated. Conclusions The repeated low doses of UVB protected to a limited extent against the effects of an erythemal UVB dose on cytokine expression and thymine dimer formation, but not on CHS or COX enzymes.

Blister development in bullous pemphigoid (BP) results from destruction of hemidesmosomes and basement membrane components within the dermoepidermal junction by autoantibodies. Adhesion molecules can take part in pathogenesis of this disease. The aim of the study was to determine the localization and expression of L- and E-selectins andβ1,β3, andβ4 integrins by immunohistochemistry in skin lesions of 21 patients with BP, compared with 10 healthy subjects. Expression of L and E selectins andβ1,β3 integrins was detected mainly in basal keratinocytes and in inflammatory infiltrates in the dermis, expression ofβ4 integrin was irregular and was detected mainly in dermal part of the blister, while in the control group only weak and single expression of the examined molecules was detected in basal keratinocytes and endothelium cells. The obtained results reveal the important role of selected selectins and integrins in development of skin lesions in BP.

Antimalarials are used to treat cutaneous and systemic lupus erythematosus (SLE). Even though cardiac damage is a rare complication, over the last decade several reports have raised the issue of cardiotoxicity associated with antimalarials. Therefore, the aim of study was to evaluate the influence of seven-month chloroquine treatment with a 250 mg daily dose on arrhythmia, conduction disturbances as well as heart rate variability and repolarization parameters assessed in 24-hour Holter monitoring. The studied group included 28 SLE patients treated with chloroquine as a monotherapy. In all the patients standard 12 leads surface ECG (50 mm) and the 24-hour ECG Holter monitoring (Oxford Medilog Excel-2) were performed before and after chloroquine phosphate treatment. All subjects presented sinus rhythm both at the enrollment and after treatment. No episodes of paroxysmal arrhythmias or conduction disturbances were reported during the study. All the patients were characterized by tendency to tachycardia, but no significant differences in mean heart rate were found before and after chloroquine administration. Similarly, no changes in heart rate variability or repolarization parameters were observed.

Fibroblasts have been implicated in psoriatic inflammatory processes. The aim of the study was to evaluate soluble interleukin 2 receptor (sIL-2R), interleukin 6 (IL-6), and interleukin 8 (IL-8) plasma levels in psoriatic patients and IL-6 and IL-8 levels in fibroblast culture supernatants. Cytokines levels in plasma and supernatants were measured by ELISA. Plasma sIL-2R, IL-6, and IL-8 levels were higher before the treatment in comparison to healthy controls (P<0.001) and decreased after treatment. Fibroblasts from healthy controls, psoriatic lesional skin, and noninvolved psoriatic skin, when stimulated with tumor necrosis factor alpha, released considerable amounts of IL-6 and IL-8. No significant difference between healthy controls and psoriatic fibroblasts was observed. Monitoring plasma sIL-2R levels could be employed as a reliable method of psoriasis activity. IL-8 and IL-6 plasma levels seem to reflect psoriasis activity, and treatment response, respectively. Fibroblasts are not a major source of increased IL-6 and IL-8 production in psoriasis.

Background/purpose: Dendritic cells (DC) play a major role in the afferent immune response. They are found as a minor cell population in the blood as three main subtypes that can be distinguished phenotypically: plasmacytoid DC (PDC), and myeloid DC1 and 2 (MDC1 and 2). The aim of the study was to examine the effect of repeated whole-body suberythemal ultraviolet (UV) B irradiation on the percentages of DC subsets in the blood and skin, and to test for photoadaptation by the subsequent administration of a local erythemal UV dose. Methods: Thirty subjects in each group were irradiated with either 0.7 personal minimal erythema dose (MED) UVB daily for 10 days (whole body), or for the 10 days followed by a single three MED UVB exposure of a local body site, or with the single three MED UVB exposure of a local body site only. Blood was collected before and after the exposures and the percentage of DC and DC subtypes assessed by flow cytometry. Skin biopsies were collected at the same times, and the number and position of the DC subsets examined by immunofluorescent microscopy. Results: The whole-body repeated UVB irradiations did not result in a change in the blood DC (BDC) or the subsets percentages in the blood, except that there was a small but significant rise in the percentage of the MDC2 subset. No alteration occurred following the local erythemal UVB exposure. The total number of BDC in the skin was small, with the PDC being located mainly in the dermis and the myeloid subtypes mainly in the epidermis. No change in cutaneous numbers or distribution was revealed following the irradiation protocols. Conclusions: Repeated whole-body suberythemal UVB irradiation does not cause a change in BDC or BDC subsets in the blood or skin, except for a small increase in the percentage of MDC2 in the blood. Local erythemal UVB irradiation does not alter the BDC subsets in blood or skin.

Recent studies point out at the role of apoptosis disturbances in the development of systemic sclerosis (SSc).The aim of our study was to examine caspase 1 and sFas serum levels in scleroderma patients and correlate the obtained results with skin involvement and internal organ changes.We studied 29 patients (14 with limited and 15 with diffuse SSc). The extension of skin involvement was measured using Total Skin Score (TSS). Internal organ involvement was assessed by specialist procedures. Serum caspase 1 and sFas levels were measured by enzyme-linked immunosorbent assay.We found correlation between sFas serum level and duration of Raynaud's phenomenon and TSS; caspase 1 serum level correlated only with TSS. Correlations between caspase 1 and lung dysfunction and sFas levels with joint and bone involvement in SSc patients were also observed.The obtained results revealed that disturbances of apoptosis might play a role in SSc pathogenesis. Caspase 1 and sFas serum levels correlate with the skin involvement severity, lung dysfunction, joint and bone changes.

The aim of our study was to analyse a significance of tumour necrosis factor (TNF)-α promoter gene polymorphisms in relation to the HLA-DR locus in genetic predisposition to pemphigus. TNF-α gene polymorphisms in position -238 and -308 were identified using a modified polymerase chain reaction-restriction fragment length polymorphism method in 53 patients with pemphigus (38 with pemphigus vulgaris, 15 with pemphigus foliaceus) and 87 healthy controls. The HLA-DRB1 locus was typed using the polymerase chain reaction SSO method in all the patients and 152 population controls.Carriers of the TNF-α polymorphic -308 A allele were found to be more frequent in the pemphigus foliaceus group in comparison with the control group (odds ratio (OR)=8.12;P=0.0005). A significant association between HLA-DRB1*04 (OR=3.86;Pcor=0.0001) and DRB1*14 (OR=8.4;Pcor=0.0001) and pemphigus vulgaris was found. In this group of patients a decreased frequency of HLA-DRB1*07 (OR=0.08;Pcor=0.006) was also identified.We have shown for the first time a positive association of TNF-α polymorphism in position -308 with pemphigus foliaceus.

Background:The association of allergic diseases, drug adverse reactions and elevated total immunoglobulin E (IgE) concentration in systemic lupus erythematosus patients remains controversial. The aim of the study was to investigate the prevalence of those features in active and inactive systemic lupus erythematosus patients, and in the control group as well.Methods:Total IgE concentration was evaluated by enzyme-linked immunosorbent assayResults and conclusions:The results of our study revealed that concomitant allergic diseases were not more frequent in systemic lupus erythematosus patients than in the general population. Total IgE concentration was significantly higher during the active stage of the disease. Drug reactions were very frequent but not connected with IgE elevation. Our results indicate that IgE may play a role in lupus pathogenesis, especially in the active phase of the disease.