Rheumatoid Arthritis: Kiraz S

Ertenli I, Kiraz S, Oztürk MA, Haznedaroğlu I, Celik I, Calgüneri M. · Department of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey. · Rheumatol Int. · Pubmed #12634936 No free full text.

Abstract: Rheumatoid arthritis (RA) is frequently complicated by thrombocytosis correlated with disease activity. The exact pathogenetic mechanism(s) that cause increased platelet counts in RA are still unknown. Recent investigations indicate that proinflammatory pleiotropic cytokines of RA also have megakaryocytopoietic/thrombopoietic properties. Moreover, several lineage-dominant hematopoietic cytokines can also act as acute phase responders and contribute to the inflammation. This review focuses on the current literature and our experience regarding the dual relationships of the pathologic thrombopoiesis of RA. Growth factors contributing to it, namely interleukin (IL)-6, IL-11, stem cell factor, leukemia inhibitory factor, granulocyte colony stimulating factor, thrombopoietin (TPO), and the regulation of megakaryocytopoiesis during the inflammatory cascade are reviewed. Some data indicate that thrombopoietin could contribute to the reactive thrombocytosis of RA. In the non-lineage-specific gp130 cytokine family, IL-6 appears to predominate for the induction of megakaryopoiesis. However, other cytokines and growth factors may also contribute to the pathologic megakaryocytopoiesis of RA. Those pleiotropic mediators seem to act in concert to regulate this enigmatic process. Clarification of the pathobiologic basis of thrombopoiesis in RA may improve understanding of the disease pathogenesis and management of the inflammatory thrombocytosis.

Cobankara V, Ozatli D, Kiraz S, Oztürk MA, Ertenli I, Türk T, Apras S, Haznedaroglu IC, Calgüneri M. · Department of Rheumatology, Pamukkale University, Medical School, Bursa Caddesi No: 119 Kinikli, Denizli, Turkey. · Clin Rheumatol. · Pubmed #15278755 No free full text.

Abstract: The aim of this study was to investigate the changes in serum levels of endothelial cell injury markers, soluble (s) E-selectin and thrombomodulin (TM), in patients with rheumatoid arthritis (RA) before and after antirheumatic drug treatment and to assess the relationship between these changes and clinical responses to the drug treatment. Eleven patients with RA having active arthritis and 12 healthy volunteers were enrolled in the study. They were monitored by clinical and laboratory parameters while receiving a combination of methotrexate, hydroxychloroquine and sulphasalazine. Pre- and post-treatment clinical and laboratory parameters, including sE-selectin and sTM levels, were measured. The ages of the patients were comparable with those of the control groups. Significant improvements were detected in erythrocyte sedimentation rate, C-reactive protein, hemoglobin, morning stiffness, patients' global assessment, physicians' global assessment, number of tender joints and number of swollen joints improved at the end of the therapy (for each parameter p < 0.05). Significant improvements were detected in clinical and laboratory parameters. In the patient group there were significant decreases in the levels of sTM and sE-selectin after treatment (p < 0.05). The patient group had significantly higher sTM and sE-selectin levels than the control group at the beginning of the study (p < 0.01), but the difference returned to normal after the treatment (p > 0.05). The sE-selectin and sTM levels significantly correlated with each other, and also with clinical and laboratory findings. Combination treatment successfully treated RA patients. sE-selectin and sTM levels probably reflect disease activity and can be helpful in monitoring disease status and response to therapy.

Calgüneri M, Pay S, Calişkaner Z, Apraş S, Kiraz S, Ertenli I, Cobankara V. · Hacettepe University School of Medicine, Department of Rheumatology, Ankara, Turkey. · Clin Exp Rheumatol. · Pubmed #10609068 No free full text.

Abstract: OBJECTIVE: The response to single disease modifying antirheumatic drug (DMARD) is often suboptimal in patients with rheumatoid arthritis (RA). Thus, despite the limited data on the therapeutic efficacy of combination therapies, many patients are currently treated with a combination of DMARDs. METHODS: We studied prospectively the efficacy of combination therapy with DMARDs. The study was designed as a randomized trial and a single DMARD or two or three DMARD combinations were administered to 180 consecutive, age- and sex-matched patients with active RA, each of whom was followed up for a period of 2 years under treatment. Patients were divided into 3 groups which did not differ with regard to demographic, clinical and laboratory parameters. Patients in group I were treated with a single DMARD [methotrexate (MTX) 7.5-15 mg/week or sulfasalazine (SSZ) 1-2 g/day or hydroxychloroquine (HCQ) 200 mg/day], group II with MTX + SSZ or MTX + HCQ, and group III with a combination of all three drugs. Patients were re-evaluated at regular intervals by means of clinical and biochemical tests designed to detect specific rheumatic activity. Radiological assessments were also performed and scored according to Larsen by the same radiologist who was blinded to the treatment groups. RESULTS: At the end of the trial there were significant improvements in the clinical and laboratory parameters in all 3 groups. However, improvements were greater and much more significant in the patients who were given combination therapies. The combination of MTX + SSZ + HCQ was more effective than both monotherapy and the two-drug combinations. CONCLUSION: In conclusion, we suggest that patients with RA should be treated with combinations of DMARDs.

Ertenli I, Kiraz S, Ertürk H, Haznedaroglu IC, Celik I, Calgüneri M, Kirazli S. · Department of Internal Medicine, Hacettepe University Medical School, Ankara, Turkey. · J Rheumatol. · Pubmed #10493673 No free full text.

Abstract: OBJECTIVE: To investigate circulating thrombopoietin (TPO) concentrations in systemic sclerosis (SSc). METHODS: TPO concentrations were measured by ELISA in serum samples of 13 patients (11 female, 2 male) with diffuse SSc, 15 healthy controls (13 female, 2 male), and 15 patients (13 female, 2 male) with rheumatoid arthritis (RA). Thrombocyte counts of patients with SSc and RA and controls were recorded. RESULTS: Median TPO concentrations were 115 (164) in SSc, 76 (32) in RA, and 62 (34) pg/ml in controls. Median serum TPO concentration in the SSc group was significantly higher than other groups; there was no difference between controls and patients with RA (p<0.001 for both comparisons). Median platelet counts of SSc, RA, and controls were 224+/-58x10(9)/l, 238+/-44x10(9)/l, and 272+/-35x10(9)/l, respectively. There was no correlation between thrombocyte counts and TPO levels in any group. CONCLUSION: We show that patients with SSc have higher serum TPO concentrations compared to healthy controls and patients with RA. It can be hypothesized that TPO mediated release of particular growth factors may participate in the pathogenesis of the fibrotic process of SSc.

Kisacik B, Tufan A, Kalyoncu U, Karadag O, Akdogan A, Ozturk MA, Kiraz S, Ertenli I, Calguneri M. · Hacettepe Medical Faculty, Rheumatology Department, Ankara, Turkey. · Joint Bone Spine. · Pubmed #18403245 No free full text.

Abstract: AIMS: The aim of this retrospective study was to investigate the correlation between MPV and the clinical disease activity indices of rheumatoid arthritis and ankylosing spondylitis. METHODS: The study consisted of 32 active RA patients (males/females: 7/25, mean age: 49+/-13) and 30 active AS patients (males/females: 15/15, mean age: 36+/-12) along with 26 osteoarthritis (OA) patients (males/females: 4/22, mean age: 52+/-8) and 29 age-matched healthy subjects (males/females: 5/24, mean age: 41+/-7) as control groups for RA and AS, respectively. RESULTS: MPV was significantly lower in both AS patients and RA patients with active disease as compared to controls (RA vs OA p<0.001, AS vs healthy subjects p<0.001). After treatment MPV values significantly increased in AS and RA (p<0.001 for all). However, MPV values remained somewhat lower in RA patients than OA patients (p=0.019). There was a negative correlation between MPV values and BASDAI scores in AS patients after two months of treatment (r=-0.507; p=0.004). CONCLUSION: Our results suggest that assessment of MPV may provide additional information about inflammation in AS and RA.

Calgüneri M, Ureten K, Akif Oztürk M, Onat AM, Ertenli I, Kiraz S, Akdogan A. · Hacettepe University Department of Rheumatology, Ankara, Turkey. · Clin Exp Rheumatol. · Pubmed #16870099 No free full text.

Abstract: OBJECTIVE: Presence of extra-articular manifestations (EAM) in rheumatoid arthritis (RA) is associated with more severe disease and increased mortality. Prevalence of EAM may vary in different geographic areas and in different ethnic populations. In this study we investigated the frequency of EAM in 526 RA patients from a single university hospital in Turkey. METHODS: The hospital records of patients who had been diagnosed as RA in Hacettepe University Department of Rheumatology between the years 1988 and 2003 were retrospectively evaluated. There were 73 males and 453 females, and mean age of the patients was 48.0 +/- 12.3 years. The mean follow-up period was 4.8 +/- 4.1 years. Three hundred and fifty-nine patients were rheumatoid factor (RF) positive (68.3%). RESULTS: The overall frequency of EAM was 38.4% (202 patients). The most common EAM was rheumatoid nodules (18.1%). Sicca symptoms, pulmonary findings, Raynaud's phenomenon, livedo reticularis, carpal tunnel syndrome, vasculitis, amyloidosis, and Felty syndrome were present in 11.4%, 4.8%, 3%, 4.8%, 2.8%, 1.3%, 1.1%, and 0.3% of the patients, respectively. Overall EAM and rheumatoid nodules were significantly more common in RF positive patients than RF negative patients. The frequency of rheumatoid nodules was significantly higher in males than in females. CONCLUSION: The prevalence of EAM in Turkey is higher than East Asia and Africa, and lower than UK and North America. Excluding secondary Sjögren's syndrome, our results are similar to other Mediterranean populations like Italy.

Pay S, Türkçapar N, Kalyoncu M, Simşek I, Beyan E, Ertenli I, Oztürk MA, Düzgün N, Erdem H, Ozbalkan Z, Kiraz S, Kinikli G, Besbas N, Dinç A, Ateş A, Olmez U, Calgüneri M, Aydintuğ OT, Bakkaloğlu A, Turan M, Turgay M, Karaaslan Y, Topaloğlu R, Duman M, Ozen S, Anonymous00040. · Division of Rheumatology, Gulhane Military School of Medicine, Ankara, Turkey. · Clin Rheumatol. · Pubmed #16365690 No free full text.

Abstract: Adult-onset Still's disease (AOSD) has often been regarded as the adult spectrum of systemic juvenile idiopathic arthritis (sJIA). The present study aims to compare the clinical and laboratory features, the disease course and the response to treatment in patients having AOSD with those having sJIA. Retrospective review of all available data that were filled out by adult and paediatric rheumatologists from six centers using a standard data extraction form was performed. A total of 95 patients with AOSD and 25 patients with sJIA were recruited for the study. The frequency of fever, rash, myalgia, weight loss and sore throat was higher in patients with AOSD. The pattern of joint involvement differed slightly. Laboratory findings were similar in both groups, except that liver dysfunction and neutrophilia were more common among adults. A multiphasic pattern dominated the childhood cases, whereas the most frequent course was a chronic one in adults. Corticosteroids and methotrexate were the most commonly employed therapy; however, chloroquine was another popular therapy in the adult group. We showed a difference in the rate of clinical and laboratory features between patients with AOSD and those with sJIA. AOSD and sJIA may still be the same disease, and children may simply be reacting differently as the result of the first encounter of the putative antigens with the immune system.

Cobankara V, Oztürk MA, Kiraz S, Ertenli I, Haznedaroglu IC, Pay S, Calgüneri M. · Department of Rheumatology, Pamukkale University School of Medicine, Denizli, Turkey. · Rheumatol Int. · Pubmed #15761728 No free full text.

Abstract: Local functional renin-angiotensin systems (RAS) have been demonstrated in many organ and tissue systems. Angiotensins, the effector growth factors of the RAS, are essentially cytokines and growth factors which actively contribute to many inflammatory reactions. Among the components of RAS, angiotensin-converting enzyme (ACE) and renin have been previously investigated separately in RA. In this study, ACE levels and renin concentrations were measured in the sera of 16 patients with RA (median age: 45 (26-69), male/female: 3/13), 13 patients with osteoarthritis (OA) (median age: 55 (28-72), male/female: 5/8), and 11 healthy adults (median age: 44 (35-70), male/female: 6/5). Synovial ACE levels and renin concentrations were also measured concurrently in patients with RA and OA. Serum ACE levels were comparable between the groups. However, synovial fluid ACE levels were significantly higher in the patients with RA than in patients with OA. Likewise, synovial fluid renin concentrations were higher in RA patients than in OA patients, while serum renin concentrations were similar in patients with RA and OA and in healthy controls. Moreover, there was a significant negative correlation between the duration of the disease and synovial renin concentrations in RA patients. In conclusion, locally-generated active renin and ACE could contribute to joint destruction in rheumatoid arthritis.

Calgüneri M, Oztürk MA, Ozbalkan Z, Akdogan A, Ureten K, Kiraz S, Ertenli I. · Department of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey. · J Int Med Res. · Pubmed #12964513 No free full text.

Abstract: This study aimed to assess the frequency of all palpable lymph nodes during active disease and remission in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Hospital records of 100 SLE patients, 100 RA patients, 100 spondyloarthropathy patients, and 150 osteoarthritis patients, treated in our rheumatology department, were evaluated retrospectively. Overall frequencies of enlarged lymph nodes in patients with active RA and SLE were 82% and 69%, respectively. Enlarged lymph nodes associated with RA were mostly located in the axillary region, and in SLE the nodes were smaller and lymphadenopathy was more generalized compared with RA. Palpable lymph nodes disappeared in the majority of patients during remission. Lymphadenopathy was significantly less frequent in patients treated with steroids before admission. Lymph node enlargement is an important physical finding associated with RA and SLE disease activity. Atypical locations and unusually large lymph nodes should raise clinical suspicion of another underlying disease.

Oztürk MA, Ertenli I, Kiraz S, C Haznedaroğlu I, Celik I, Kirazli S, Calgüneri M. · Department of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey. · Rheumatol Int. · Pubmed #12750940 No free full text.

Abstract: Behçet's disease (BD) commonly presents with articular manifestations and thrombotic vasculopathy. Arthritis of BD characteristically demonstrates a recurrent and nondestructive course. The pathobiological basis of the thrombotic vasculopathy and protective factors against cartilage destruction in arthritis of BD have not been elucidated. Apart from being involved in fibrinolysis and thrombolysis, the plasminogen activation system can contribute to the pathogenesis of destructive joint diseases such as rheumatoid arthritis (RA). Plasminogen activator inhibitor-1 (PAI-1) is a well known fibrinolysis inhibitor. In this study, local synovial fluid and circulating plasma PAI-1 concentrations of BD were assessed in comparison to RA patients and healthy controls to investigate the nonerosive, nondestructive nature of Behçet arthritis. Twelve patients with BD (mean age 34+/-11 years, males:females 6:6), 15 with RA (mean age 36+/-8 years, males:females 3:12), and 15 healthy adults (mean age 32+/-10 years, males:females 6:9) were included in this study. Plasma PAI-1 antigen levels and PAI-1 activities were significantly greater in BD patients than in RA patients and healthy controls ( P<0.001). Synovial fluid levels of both parameters were also higher than in RA patients ( P<0.001). These results suggest that PAI-1 may promote hypofibrinolysis of Behçet's vasculopathy and also have a protective role in the arthritis of BD.

Kiraz S, Ertenli I, Oztürk MA, Haznedaroğlu IC, Celik I, Kirazli S, Calgüneri M. · Hacettepe University School of Medicine, Ankara, Turkey. · Clin Rheumatol. · Pubmed #12447626 No free full text.

Abstract: Thrombopoietin (TPO) is the major regulator of growth and differentiation of megakaryocytes. Recent studies have shown that TPO may also act as an acute-phase reactant, and it has been suggested as a component of inflammatory reactions. In this study our objective was to investigate serum TPO levels in patients with rheumatoid arthritis, a complex chronic inflammatory disorder not uncommonly associated with thrombocytosis. Bloodstream TPO concentrations were assessed in 13 RA patients with platelet counts between 450 and 650 x 10(9)/l, 10 RA patients with platelet counts >650 x 10(9)/l, 15 RA patients with normal platelet counts and 12 healthy controls. RA patients with normal platelet counts had TPO levels comparable with healthy controls. TPO concentrations in patients with mild thrombocytosis were significantly elevated, whereas patients with markedly increased thrombocyte counts had prominently decreased TPO levels. These results indicate that TPO seems to be associated with reactive thrombocytosis in RA patients with active disease. In patients with extremely increased thrombocytosis serum TPO levels might be regulated by increased platelet mass via receptor-mediated uptake and metabolism.

Ertenli I, Kiraz S, Calgüneri M, Celik I, Erman M, Haznedaroglu IC, Kirazli S. · Department of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey. · Clin Exp Rheumatol. · Pubmed #11760396 No free full text.

Abstract: OBJECTIVE: To investigate the synovial fluid levels of interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), IL-1 receptor antagonist (IL-1ra), soluble IL-2 receptor (sIL-2r) and IL-8 in patients with Behçet's disease (BD) and to compare them to levels in rheumatoid arthritis (RA), and osteoarthritis (OA). METHODS: The cytokine levels of BD (n = 14), RA (n = 15) and OA (n = 15) patients were assessed by enzyme-linked immunosorbent method. RESULTS: Median synovial IL-1 beta and TNF-alpha levels were higher in RA compared to BD and OA patients. IL-1 beta levels were also higher in BD than OA whereas TNF levels were similar in these two groups. IL-1ra and TGF-beta activity in BD were higher than OA but lower than RA. sIL-2r and IL-8 levels were increased in BD and RA in comparison to OA patients. CONCLUSION: The arthritis of BD is non-erosive and accordingly, its synovial fluid contains lower levels of cytokines primarily involved in cartilage destruction, namely IL-1 beta and TNF-alpha, than RA. IL-1ra and TGF might serve as protective factors against erosion in the inflamed joints. High synovial fluid levels of sIL-2r and IL-8 probably reflect a non-specific inflammatory process.