Jarosław Bogaczewicz

Vitamin D effects in atopic dermatitis

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)D3 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)D₃ 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 < .05). 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.

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)D3 were measured with electrochemiluminescence immunoassay (ECLIA). Enzyme-linked immunosorbent assays (ELISA) were used to determine antibodies directed against 1,25(OH)2D3 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)D3 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)D3 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)D3 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)2D3 were detected in three SLE patients. No significant difference in 25(OH)D3 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)2D3 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)2D3 antibodies, but these antibodies do not appear to affect vitamin D levels.

Serum Concentration of Interleukin-6 Is Increased Both in Active and Remission Stages of Pemphigus Vulgaris

As most studies on pemphigus vulgaris (PV) pathogenesis concern its active stage, we aimed to evaluate the serum concentration of TNF-α, IL-1, and IL-6 in PV patients in clinical remission. The study group consisted of sera from 19 PV patients in active stage and from 24 patients in clinical remission. 19 sera taken from healthy subjects served as the controls. Serum IL-6 concentrations in PV active and PV remission group were significantly higher when compared to the controls (P < .05). In patients in active stage of PV, a significant correlation between serum IL-1 and IL-6 concentrations was found (r P = 0.46; P < .05). We also found a negative correlation between TNF-α level and pemphigus antibodies titer in the patients from the remission group (r S = −0.47303; P < .02). Our data suggest that IL-6 and TNF-α may be involved in maintaining immunological disturbances in remission stage of PV.

The Imbalance in Serum Concentration of Th-1- and Th-2-Derived Chemokines as One of the Factors Involved in Pathogenesis of Atopic Dermatitis

Atopic dermatitis (AD) is an inflammatory skin disease in which pathogenesis chemokines are partially involved. The aim of the paper was to assess the serum level of CXCL-9, CXCL-10, CXCL-11, CXCL-12, CCL-17, CCL-20, CCL-21, CCL-22, CCL-27, and IL-18 chosen in AD patients by ELISA assay. Forty patients (mean age 11.4 years old) with AD and 50 healthy controls were enrolled into the study. The patients and controls were divided into two age categories: under 10 years old (Group 1 and Control 1) and over 10 years old (Group 2 and Control 2). Significantly lower serum concentration of CXCL-9, CXCL-10, CCL-17, and IL-18 and higher concentration of CXCL-12 and CCL-27 were found in Group 1 when compared to Control 1. In Group 2 serum concentration of CXCL-12, CCL-17, CCL-22 was higher than in Control 2. The obtained results indicate the imbalance in chemokine serum levels in AD what suggests their role in the disease pathogenesis.

Vitamin D Receptor Gene BsmI Polymorphism in Polish Patients with Systemic Lupus Erythematosus

The hormonally active form of vitamin D3, 1,25(OH)2D3 (calcitriol), exerts actions through VDR receptor, which acts as a transcriptional factor. Calcitriol is an immunomodulator that affects various immune cells, and several studies link it to many autoimmune diseases. BsmI polymorphism affects the level of VDR gene transcription, transcript stability, and posttranscriptional modifications. It seems to be related to the systemic lupus erythematosus (SLE). Our study examined the characteristics of VDR gene BsmI polymorphism in Polish SLE patients and their relationship with clinical manifestations of the disease. We genotyped 62 patients with SLE and 100 healthy controls using the real-time PCR. There were no differences observed in the frequency of BsmI genotypes in SLE patients and in the control group. There was no significant correlation between BsmI genotypes and clinical symptoms of SLE, but the AA genotype correlates with higher levels of antinuclear antibodies (ANA) in this group (r = 0.438; P = 0.002). A larger study examining BsmI and other VDR gene polymorphisms is needed. It may allow explaining differences in the clinical picture of the disease and choosing a personalized therapy.

Clinical and psychological characteristics of patients with psoriasis reporting various frequencies of pruritus

Pruritus is a common subjective symptom of psoriasis whose levels may be affected by a range of variables. The objective of this study was to evaluate the frequency of pruritus and its associations with clinical and psychological characteristics of psoriasis patients.

Contact hypersensitivity to haptens of the European standard series and corticosteroid series in the population of adolescents and adults with atopic dermatitis.

BackgroundUntil recently, it was thought that in patients with atopic dermatitis (AD), contact hypersensitivity phenomenon occurs less frequently than in the general population because of the impaired cellular immune response. ObjectiveThe aim of this study was to evaluate the incidence of contact dermatitis in the population of patients with AD. MethodsA total of 39 patients with clinical diagnosis of AD during remission were patch tested with 28 European Baseline Series allergens and 8 corticosteroids allergens in different concentrations and media. Twenty-nine (74.3%) patients were female and 10 (25.6%) patients were male. Thirty-three (84.6%) patients were older than 18 years. The mean duration of AD was 20 years. ResultsNineteen (48%) patients had an allergic reaction to at least 1 European Standard Series allergen, and 5 (12.8%) patients had an allergic reaction to at least 1 corticosteroid. The most common allergens giving positive results were nickel sulfate (28.2%), potassium dichromate (20.5%), cobalt chloride (12.8%), and phenylenediamine, budesonide, betamethasone, clobetasol, and dexamethasone (7.7% each). ConclusionsThis study shows that allergic contact hypersensitivity is common among patients with AD and affects up to 40% of cases. Contact allergy to corticosteroids becomes a serious problem in the treatment of chronic inflammatory dermatoses such as AD.

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.

Vitamin D receptor gene polymorphism Fok I in the Polish population does not contribute to the risk of systemic lupus erythematosus

Sir, Recent studies have suggested that the vitamin D receptor (VDR) gene polymorphism may be involved in genetic predisposition toward susceptibility to development of autoimmune diseases such as rheumatoid arthritis. Fok I polymorphism is due to transition C instead of T nucleotide in a promoter region and results in greater transcriptional activity of VDR. Enhanced expression of the VDR gene may possibly affect the expression of other genes containing such a VDR response element, and in turn it may lead to dysregulation of the Th1/Th2 balance with subsequent greater risk of development of the autoimmune process. On the other hand, the VDR gene may not be responsible for the primary association with inflammation and autoimmunity but may be in linkage disequilibrium with a nearby novel disease-related locus. In systemic lupus erythematosus (SLE) reports concerning the role of Fok I are even more sparse than in rheumatoid arthritis. In the study by Huang et al., no essential differences in the frequency of Fok I between 52 patients with SLE and with the control group were revealed, though the patients were limited to an Asian population. In accordance with the latter in a recent study by Monticielo et al., no significant association was found in genotype and allelic frequencies of Fok I polymorphism between European-derived cases and controls in Brazilian patients with SLE. We studied 62 patients with SLE and 100 healthy individuals (Table 1). Genotyping of Fok I (rs2228570) VDR polymorphism was performed by real-time polymerase chain reaction with the simple probe. The genotype frequencies in the control group were consistent with the Hardy-Weinberg equilibrium; however, in SLE they were not ( 1⁄4 0.53; p1⁄4 0.46 and 1⁄4 4.14; p1⁄4 0.04, respectively). The comparison of the frequency of Fok I VDR genotypes based on the analysis with the 2 test did not reveal any essential difference between SLE patients and the control group. Our results corroborate both aforementioned studies, as the possible risk of SLE imputed to Fok I VDR gene polymorphism assessed by logistic regression analysis did not significantly differ in the group of Caucasian patients when compared to the healthy individuals. In assessing the association between VDR Fok I polymorphism and clinical and laboratory features of SLE,Monticielo et al. found no statistical significance. It remains in accordance with our results as no difference in the risk of development of a given clinical manifestation of SLE between genotypes of Fok I VDR gene was revealed. Several other factors such as variable sample size and ethnicity may also contribute toward contradictory results, therefore further and larger studies are required. In general, single nucleotide polymorphism in a given gene may not only lead to amino acid substitution altering protein function but also may cause altered splicing, and disruption of exonic splicing enhancer sequences or exonic mRNA stability/instability sequences. The VDR gene promoter directs the transcription of at least three VDR mRNA transcripts in the kidney that seem to arise from the differential splicing of 5’-noncoding exons. Thus VDR is regulated at both transcriptional and posttranscriptional levels. Alternative splicing of the retinoid receptor, thyroid hormone receptor, and other receptors is a common feature of this gene family of proteins. Interestingly, the VDR gene is induced with retinoic acid at a site that lies downstream of exon 1, and it is likely that this site mediates the recognition ability of induction of the transcription of VDR. Therefore additional studies require both genetic analysis in multiple ethnic groups and environmental influences in order to determine the overlapping and unique associations among genetic polymorphisms. In conclusion, in the Polish population of patients Fok I polymorphism appears not to increase the risk of SLE.

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 β 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.