National Institute of Rheumatic Diseases

Piešťany, Slovakia

National Institute of Rheumatic Diseases

Piešťany, Slovakia
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Gabrhel J.,Private Clinic of Rehabilitation Medicine | Popracova Z.,National Institute of Rheumatic Diseases | Tauchmannova H.,National Institute of Rheumatic Diseases | Chvojka Z.,Private Clinic of Medical Rehabilitation
Thermology International | Year: 2012

The authors describe various thermographic and musculoskeletal ultrasound images of the painful knee syndrome, using the images for differential diagnosis of various types of injuries and diseases of the knee such as socalled "growth pain", rheumatoid and other types of arthritis, aseptic necrosis, hydrops or haemarthrosis of the knee joint due to distorsion, distension or ligament rupture, bursopathy, cysts, enthesiopathy or sympathetically maintained pain. The combination of both methods seems to be most accurate in assisting diagnosis. Musculoskeletal ultrasound images inform about the structural changes of a painful knee. Thermographic images provide information on the pathophysiology of the pain by recording the temperature distribution on the knee surface. The level of temperature may be related to inflammatory reactions or to the activity of efferent nociceptive sympathetic nerve fibers. Information obtained via thermographic and musculoskeletal ultrasound examinations are important in making decisions on adequate treatment and rehabilitation.

Stark K.,University of Regensburg | Straub R.H.,University of Regensburg | Rovensky J.,National Institute of Rheumatic Diseases | Blazickova S.,National Institute of Rheumatic Diseases | And 3 more authors.
Arthritis Research and Therapy | Year: 2015

Introduction: Rheumatoid arthritis (RA) is characterized by decreased androgen levels, which was the first hormonal abnormality described. Several studies indicated that steroidogenesis is directed towards endogenous glucocorticoids at the expense of androgens. The decisive step governing androgen synthesis is the 17,20-lyase activity of the CYP17A1 gene-encoded enzyme cytochrome P450 17A1. Here, we focused on the role in RA of the critical cofactor for 17,20-lyase activity, cytochrome b5, encoded by the CYB5A gene. Methods: Data sets of two genome wide RA association studies (GWAS) were screened for single nucleotide polymorphisms (SNP) in the CYB5A gene. Candidate SNPs in CYB5A were studied in a case-control study population of Slovakia. Expression analyses were done in synovial fibroblasts from RA patients by quantitative real-time polymerase chain reaction, and cytochrome b5-expression was detected by immunohistochemistry. Real-life androgen production after steroid conversion was measured using radiolabeled substrates. Results: The study identified the RA-associated intronic SNP rs1790834 in the CYB5A gene in one GWAS and confirmed the same SNP in our study. The minor allele reduced RA risk selectively in women (P = 4.1*10-3; OR = 0.63, 95% CI [0.46-0.86]). The protective effect was confined to rheumatoid factor-positive (OR = 0.53, [0.37-0.75]) and anti-cyclic citrullinated peptide-positive (OR = 0.58, [0.41-0.83]) cases, respectively. The protective allele doubles CYB5A mRNA-expression resulting in 2-3fold activation of steroid 17,20-lyase activity, and protective allele was accompanied by a higher density of cytochrome b5-positive cells in synovial tissue. Conclusions: CYB5A is the first RA susceptibility gene involved in androgen synthesis. Our functional analysis of SNP rs1790834 indicates that it contributes to the sex bias observed in RA. © Stark et al.; licensee BioMed Central.

Gabrhel J.,Private Clinic of Rehabilitation Medicine | Tauchmannova H.,National Institute of Rheumatic Diseases | Chvojka Z.,Private Clinic of Medical Rehabilitation
Thermology International | Year: 2010

OBJECTIVE: Thermal images of the lumbar and gluteal area were analysed retrospectively in a group of 141 patients (77 male, 64 female, mean age:43.2 years) suffering from pain in the lumbar and sacral region. Patients with post-traumatic and rheumatic disorders were excluded. In all 141 patients, X-rays, CTs and MRIs were carried out. Ultrasound scans and laboratory examinations were performed in patients with urogenital ailments. RESULTS: The majority of 28 patients with structural changes in the lower back area (discopathy, facet syndrome) showed in their thermal images various hyperthermal patterns over the lumbar spine and paravertebral areas. In patients with urogenital findings, hypothermal areas over the lateral parts of the lumbosacral (LS) region and parasacral areas were found as a consequence of the viscero-reflexive autonomic reaction. 89 patients, who presented with painful manifestations but without structural and urogenital disorders, showed active thermal findings in small sites in the gluteal area caused by local trigger points and over the crista iliaca due to enthesopathy. A small number of these patients with functional disorders showed hypothermal patterns over the spine and in the paravertebral region. A high sensitivity of thermography was observed among patients with structural and urogenital findings. Low specificity of this method was revealed in patients with structural findings of the lower back. Due to different thermal changes caused by functional and structural disorders of the lower back and rare thermal findings after urogenital disease, these disorders can be differentiated with high sensitivity, but low specificity. High specificity was only observed in patients with a history of urogenital diseases and absence of hyperthermic changes. CONCLUSION: The thermographic examination is assists in identification of the affected region and for assessing whether the thermal changes originate from a functional disorder or an inflammation. In this respect, it offers a solid basis for further diagnostics and adaequat treatment.

Duru N.,University Utrecht | Van Der Goes M.C.,University Utrecht | Jacobs J.W.G.,University Utrecht | Andrews T.,EULAR Social Leagues Patients Representative | And 12 more authors.
Annals of the Rheumatic Diseases | Year: 2013

To develop recommendations for the management of medium to high-dose (ie, >7.5 mg but 7le;100 mg prednisone equivalent daily) systemic glucocorticoid (GC) therapy in rheumatic diseases. A multidisciplinary EULAR task force was formed, including rheumatic patients. After discussing the results of a general initial search on risks of GC therapy, each participant contributed 10 propositions on key clinical topics concerning the safe use of medium to high-dose GCs. The final recommendations were selected via a Delphi consensus approach. A systematic literature search of PubMed, EMBASE and Cochrane Library was used to identify evidence concerning each of the propositions. The strength of recommendation was given according to research evidence, clinical expertise and patient preference. The 10 propositions regarded patient education and informing general practitioners, preventive measures for osteoporosis, optimal GC starting dosages, risk-benefit ratio of GC treatment, GC sparing therapy, screening for comorbidity, and monitoring for adverse effects. In general, evidence supporting the recommendations proved to be surprisingly weak. One of the recommendations was rejected, because of conflicting literature data. Nine final recommendations for the management of medium to high-dose systemic GC therapy in rheumatic diseases were selected and evaluated with their strengths of recommendations. Robust evidence was often lacking; a research agenda was created.

Imrich R.,Slovak Academy of Sciences | Rovensky J.,National Institute of Rheumatic Diseases
Rheumatic Disease Clinics of North America | Year: 2010

The hypothalamic-pituitary-adrenal (HPA) system is a powerful neuroendocrine control mechanism involved in many core body functions including metabolic and energy homeostasis. The HPA axis has been considered an important immune modulator primarily in view of potent anti-inflammatory effects of cortisol in high physiologic and pharmacologic doses. This article describes HPA's role in rheumatoid arthritis. © 2010 Elsevier Inc.

Ruedel A.,University of Regensburg | Stark K.,University of Regensburg | Kaufmann S.,University of Regensburg | Bauer R.,University of Regensburg | And 5 more authors.
FASEB Journal | Year: 2014

Osteoarthritis (OA) is the most common form of arthritis. It is characterized by cartilage destruction and bone remodeling, mediated in part by synovial fibroblasts (SFs). Given the functional significance of cadherins in these cells, we aimed at determining the role of genetic variants of N-cadherin (CDH2) in OA of the knee and hip. Six single-nucleotide polymorphisms in the genomic region of the CDH2 gene were genotyped in 312 patients with OA and 259 healthy control subjects. Gene expression of CDH2 was analyzed by qRT-PCR. Liquid chromatography-mass spectrometry was used to identify a transcription factor isolated by DNA pulldown. Its potential for binding to gene variants was examined by electrophoretic mobility shift assay, enzyme-linked immunosorbent assay, and chromatin immunoprecipitation. Genetic analysis identified a polymorphism located in the CDH2 promoter region to be associated with risk of OA. The minor allele of rs11564299 had a protective effect against OA. Compared to carriers of the major allele, carriers of the minor allele of rs11564299 displayed increased Ncadherin levels in SFs. Based on in silico analysis, the minor allele was predicted to generate a novel transcription factor binding site, Direct-binding assays and mass spectrometric analysis identified hnRNP K as binding selectively to the minor allele. In summary, a CDH2 promoter polymorphism influences the risk of OA, and hnRNP K was found to be involved in the regulation of elevated N-cadherin expression in patients with OA carrying the minor allele of rs11564299. © FASEB.

Rovensky J.,National Institute of Rheumatic Diseases | Imrich R.,Slovak Academy of Sciences | Lazurova I.,Pavol Jozef Safarik University | Payer J.,Comenius University
Annals of the New York Academy of Sciences | Year: 2010

The article summarizes reports on the concurrence of Klinefelter's syndrome (KS) with inflammatory rheumatic diseases, rheumatoid arthritis (RA), juvenile idiopathic arthritis, psoriatic arthritis, polymyositis/dermatomyositis, systemic lupus erythematosus, systemic sclerosis, mixed connective tissue disease, the antiphospholipid syndrome, and ankylosing spondylitis. These include two case reports of patients with KS concurrently associated with RA or antisynthetase syndrome, respectively, previously reported by the author and his coworkers. Attention is paid to the pathogenesis and the course of the disease in patients with KS. The importance of early diagnosis of the syndrome, when occurring simultaneously with other diseases of connective tissue, is emphasized. © 2010 New York Academy of Sciences.

Stark K.,University of Regensburg | Straub R.H.,University of Regensburg | Blazickova S.,National Institute of Rheumatic Diseases | Hengstenberg C.,University of Regensburg | Rovensky J.,National Institute of Rheumatic Diseases
Annals of the New York Academy of Sciences | Year: 2010

Both genetic and environmental factors contribute to rheumatoid arthritis (RA) as well as osteoarthritis (OA). For RA, most of the known genetic markers are linked with genes from immunological pathways. Recent genome-wide association studies (GWAS) on RA identified known and novel susceptibility genes like HLA-DRB1, PTPN22, STAT4, TRAF1/C5, OLIG3/TNFAIP3, CD40, CCL21, MMEL1-TNFRSF14, CDK6, PRKCQ, IL2RB, and KIF5A-PIP4K2C. These association signals explain more than 50% of the genetic influence on RA. In contrast, less GWAS data for OA exist. Most OA susceptibility genes arose from classical candidate gene analyses and were not replicated in all study samples. Neuroendocrine factors are hypothesized to play an important role both in RA and OA etiology. Here, we discuss these findings and present an outlook for genetic association studies after GWAS. © 2010 New York Academy of Sciences.

Sieper J.,Rheumatology | Srinivasan S.,Merck And Co. | Srinivasan S.,Celgene | Zamani O.,Rheuma Zentrum Favoriten | And 15 more authors.
Annals of the Rheumatic Diseases | Year: 2013

Objective To determine which of two referral strategies, when used by referring physicians for patients with chronic back pain (CBP), is superior for diagnosing axial spondyloarthritis (SpA) by rheumatologists across several countries. Methods Primary care referral sites in 16 countries were randomised (1 : 1) to refer patients with CBP lasting >3 months and onset before age 45 years to a rheumatologist using either strategy 1 (any of inflammatory back pain (IBP), HLA-B27 or sacroiliitis on imaging) or strategy 2 (two of the following: IBP, HLAB27, sacroiliitis, family history of axial SpA, good response to non-steroidal anti-inflammatory drugs, extraarticular manifestations). The rheumatologist established the diagnosis. The primary analysis compared the proportion of patients diagnosed with definite axial SpA by referral strategy. Results Patients (N=1072) were referred by 278 sites to 64 rheumatologists: 504 patients by strategy 1 and 568 patients by strategy 2. Axial SpA was diagnosed in 35.6% and 39.8% of patients referred by these respective strategies (between-group difference 4.40%; 95% CI -7.09% to 15.89%; p=0.447). IBP was the most frequently used referral criterion (94.7% of cases), showing high concordance (85.4%) with rheumatologists' assessments, and having sensitivity and a negative predictive value of >85% but a positive predictive value and specificity of <50%. Combining IBP with other criteria (eg, sacroiliitis, HLA-B27) increased the likelihood for diagnosing axial SpA. Conclusions A referral strategy based on three criteria leads to a diagnosis of axial SpA in approximately 35% of patients with CBP and is applicable across countries and geographical locales with presumably different levels of expertise in axial SpA.

Rovensky J.,National Institute of Rheumatic Diseases | Stancikova M.,National Institute of Rheumatic Diseases | Svik K.,National Institute of Rheumatic Diseases | Bauerova K.,Slovak Academy of Sciences | Jurcovicova J.,Slovak Academy of Sciences
Rheumatology International | Year: 2011

The purpose of this study was to evaluate the effect of β-(1,3/1,6)-d-glucan isolated from Pleurotus ostreatus (β-glucan-PO) on prophylactic treatment of adjuvant arthritis (AA) with methotrexate (MTX) in rats. Groups of rats with AA were treated with methotrexate (1 mg/kg/week), β-glucan-PO (1 mg/kg every second day) or their combination for the period of 28 days from adjuvant application. Body mass, hind paw swelling, arthrogram scores and a level of serum albumin were measured as markers of inflammation and arthritis. Treatment with low dose of MTX significantly inhibited the markers of both inflammation and arthritis. MTX and its combination with β-glucan-PO significantly increased body mass of arthritic rats. β-glucan-PO administered alone significantly decreased both the hind paw swelling and arthritic score. In combination with MTX, β-glucan-PO markedly potentiated the beneficial effects of MTX, which resulted in a more significant reduction of hind paw swelling and arthritic scores. The concentration of albumin in the serum of arthritic controls was significantly lower than in healthy controls. Both MTX alone and the combination treatment with MTX + β-glucan-PO significantly inhibited the decrease in serum albumin. β-Glucan-PO increased the treatment efficacy of basal treatment of AA with MTX. © 2009 Springer-Verlag.

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