International Journal of Rheumatology http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. The Relationship of Antibodies to Modified Citrullinated Vimentin and Markers of Bone and Cartilage Destruction in Rheumatoid Arthritis Tue, 15 Apr 2014 13:28:42 +0000 http://www.hindawi.com/journals/ijr/2014/464585/ Objective. To make individualised decisions regarding treatment is one of the most important challenges in clinical practise, and identification of sensitive and specific markers of prognosis is an important research question. The main objective of this study was to evaluate relationships between the level of autoantibodies, radiographic changes and laboratory markers of bone, and cartilage destruction. Methods. A total of 114 RA patients were examined. The serum concentration of IgM RF, antibodies to cyclic citrullinated peptide (anti-CCP), modified citrullinated vimentin (anti-MCV), matrix metalloproteinase 3 (MMP-3), and cartilage oligomeric matrix protein (COMP, ng/mL) were measured. The van der Heijde-modified Sharp Score was used to quantify the radiologic changes. Results. Among the patients who were high-positive for anti-MCV, the value of total modified Sharp score (mTSS) (96.5; 66–120) was higher as well as the joint space narrowing (82; 60.5–105.5), and a higher level of MMP-3 was recorded more frequently (56%) in comparison with negative/low-positive patients (57; 31–88, 50; 29–82, 31% resp., ). The level of COMP was also higher among patients high-positive for anti-MCV (9.7; 8.1–13.1 and 6.8; 5.4–10.7, resp., ). Conclusion. A high positive level of anti-MCV as contrasted with anti-CCP and IgM RF is associated with more pronounced destructive changes in the joints. A. S. Avdeeva, E. N. Aleksandrova, A. A. Novikov, A. V. Smirnov, M. V. Cherkasova, and E. L. Nasonov Copyright © 2014 A. S. Avdeeva et al. All rights reserved. The Relationship between Mechanical Hyperalgesia Assessed by Manual Tender Point Examination and Disease Severity in Patients with Chronic Widespread Pain: A Cross-Sectional Study Tue, 15 Apr 2014 13:10:47 +0000 http://www.hindawi.com/journals/ijr/2014/417596/ The clinical utility of tender point (TP) examination in patients reporting chronic widespread pain (CWP) is the subject of contemporary debate. The objective of this study was to assess the relationship between mechanical hyperalgesia assessed by manual TP examination and clinical disease severity. 271 women with CWP were recruited from a clinical setting. Data collection included patient-reported symptoms, health-related quality of life variables, and observation-based measures of functional ability, muscle strength, 6-minute walk, and pressure pain thresholds measured by cuff algometry. TP examination was conducted according to ACR-guidelines. Relationships between disease variables and TP count (TPC) were analyzed with logistic regression in a continuum model, allowing the TPC to depend on the included disease variables and two regression models carried out for a TPC threshold level, varying between 1 and 17. The threshold analyses indicated a TPC threshold at 8, above which a large number of disease variables became consistently significant explanatory factors, whereas none of the disease variables reached a significance level in the continuum model. These results support the premise that the presence of mechanical hyperalgesia influences symptomatology in CWP and that the severity of clinical expression is related to a threshold of TPs, rather than being part of a continuum. Kirstine Amris, Eva Ejlersen Wæhrens, Anders Jespersen, Anders Stockmarr, Robert Bennett, Henning Bliddal, and Bente Danneskiold-Samsøe Copyright © 2014 Kirstine Amris et al. All rights reserved. Carotid Intima Media Thickness as a Marker of Atherosclerosis in Ankylosing Spondylitis Mon, 07 Apr 2014 15:43:53 +0000 http://www.hindawi.com/journals/ijr/2014/839135/ Aim. Increased cardiovascular morbidity and mortality have been observed in ankylosing spondylitis because of accelerated atherosclerosis. We measured carotid intima media thickness (CIMT) as a surrogate marker of atherosclerosis in this study. Methods. In this study 37 cases of AS and the same number of matched individuals were recruited. CIMT measurements were done using B-mode ultrasound. Disease activity was assessed using Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), and Bath ankylosing spondylitis metrological index (BASMI) scores and C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels. Results. Mean age of the study groups was 29.43 ± 9.00 years. Average disease duration was 65.62 ± 54.92 months. Twenty-eight (75.68%) of cases were HLA B-27 positive. A significantly increased CIMT was observed in cases as compared to control group (0.62 ± 0.12 versus 0.54 ± 0.04; ). CIMT in the cases group positively correlated with age , duration of disease , and BASMI and negatively correlated with ESR . Conclusions. Patients of AS had a higher CIMT than those of the control group. CIMT correlated with disease chronicity. Naveen Gupta, Renu Saigal, Laxmikant Goyal, Abhishek Agrawal, Rajat Bhargava, and Arun Agrawal Copyright © 2014 Naveen Gupta et al. All rights reserved. Contact Frequency, Travel Time, and Travel Costs for Patients with Rheumatoid Arthritis Mon, 17 Feb 2014 11:56:15 +0000 http://www.hindawi.com/journals/ijr/2014/285951/ Objectives. To investigate travel time, and travel cost related to contacts with health care providers for patients with rheumatoid arthritis (RA) during a three-month period. Methods. Patient-reported travel time and travel cost were obtained from 2847 patients with RA. Eleven outpatient clinics across Denmark recruited patients to the study. Data collected included frequency, travel time and travel costs for contacts at rheumatology outpatient clinics, other outpatient clinics, general practitioners, privately practicing medical specialists, inpatient hospitals and accident and emergency departments. Results. Over a 3-month period, patients with RA had on average 4.4 (sd 5.7) contacts with health care providers, of which 2.8 (sd 4.0) contacts were with rheumatology outpatient clinics. Private car and public travel were the most frequent modes of travel. The average patient spent 63 minutes and 13 € on travelling per contact, corresponding to a total of 4.6 hours and 56 € during the 3-month period. There was great variation in patient travel time and costs, but no statistically significant associations were found with clinical and sociodemographic characteristics. Conclusion. The results show that patients with RA spend private time and costs on travelling when they seek treatment. These findings are particularly important when analyzing social costs associated with RA. Jan Sørensen, Louise Linde, and Merete Lund Hetland Copyright © 2014 Jan Sørensen et al. All rights reserved. Allopurinol, Benzbromarone, or a Combination in Treating Patients with Gout: Analysis of a Series of Outpatients Wed, 12 Feb 2014 08:53:24 +0000 http://www.hindawi.com/journals/ijr/2014/263720/ Objective. To profile a sample of gouty patients treated with allopurinol, benzbromarone, or a combination of these two drugs and to describe the impact of this therapy in reducing uric acid levels. Methods. An observational, transversal study was performed. We evaluated 48 patients diagnosed with gout who were seen at the Outpatient Rheumatology Clinic of the Federal University of Paraná between January 2009 and November 2010. Clinical data, creatinine serum levels, and basal and posttreatment levels of serum urates, transaminases, and bilirubins were recorded. Uric acid levels were measured in a 24-hour urine sample. Patients were divided into three groups: patients given only allopurinol (A), only benzbromarone (B), and both in combined therapy (A + B). Results. The average age of these patients was 56.6 ± 11.4 years, varying from 35 to 81 years. The entire patient group experienced a significant drop in serum urate levels, from 8.5 ± 1.8 mg/dL (0.472 ± 0.1 mmol/L) to 6.7 ± 2.1 mg/dL (0.372 ± 0.116 mmol/L) (), regardless of the prescribed medication. The number of patients taking both drugs whose serum uric acid values fell within normal range (men <7 mg/dL (0.38 mmol/L) and women <6 mg/dL (0.33 mmol/L)) was 85.7% (6/7) while this value for the group taking benzbromarone alone was 75% (3/4) and for the group taking allopurinol alone this number was 51.8% (14/27). Conclusions. The therapeutic combination of benzbromarone and allopurinol significantly decreased serum urate levels in patients with gout when compared to individual use of each of these agents. This finding is especially important in treating patients who cannot control hyperuricemia with monotherapy. Benzbromarone alone or in combination with allopurinol has an important clinical role in controlling hyperuricemia in patients with gout. Valderilio Feijó Azevedo, Pedro Grachinski Buiar, Laura Helena Giovanella, Carolina Rossetti Severo, and Mauricio Carvalho Copyright © 2014 Valderilio Feijó Azevedo et al. All rights reserved. A Simple Step Test to Estimate Cardio-Respiratory Fitness Levels of Rheumatoid Arthritis Patients in a Clinical Setting Mon, 23 Dec 2013 09:32:57 +0000 http://www.hindawi.com/journals/ijr/2013/174541/ Purpose. Exercise tests represent an important clinical tool to evaluate cardio-respiratory fitness and to predict future adverse cardiovascular events. However, use of such tests in patients with rheumatoid arthritis (RA) is relatively uncommon despite well-established evidence that low exercise capacity and high CVD mortality are features of this disease. Therefore, this study examined the validity and reliability of a sub-maximal step test for use in RA patients. Methods. Thirty patients (24 females) (mean ± SD age years) performed a sub-maximal step test on two occasions to estimate the criterion measure of cardio-respiratory fitness (). A further maximal cycling test provided a direct fitness measurement (). Pearson correlation coefficient, intraclass correlation coefficient (ICC), Bland and Altman plots, and 95% limits of agreement (LOA) were used to determine the validity and reliability of the sub-maximal test. Results. Estimated correlated well with directly measured (, LoA ±5.7 mL·kg−1·min−1). Test-retest reproducibility for estimated was excellent (, LoA ±2.2 mL·kg−1·min−1). Conclusion. The sub-maximal step test studied here represents a valid and reproducible method to estimate cardio-respiratory fitness in RA patients. This test may be useful for the assessment and management of CVD risk in a clinical setting. Jennifer K. Cooney, Jonathan P. Moore, Yasmeen A. Ahmad, Jeremy G. Jones, Andrew B. Lemmey, Francesco Casanova, Peter J. Maddison, and Jeanette M. Thom Copyright © 2013 Jennifer K. Cooney et al. All rights reserved. Controlled Cohort Study of Serum Gonadal and Adrenocortical Steroid Levels in Males Prior to Onset of Rheumatoid Arthritis (pre-RA): A Comparison to pre-RA Females and Sex Differences among the Study Groups Sun, 24 Nov 2013 16:19:45 +0000 http://www.hindawi.com/journals/ijr/2013/284145/ Serum testosterone levels are generally reported to be lower in male rheumatoid arthritis (RA) patients, but it is not determined if a deficiency may occur before clinical onset of disease (pre-RA). Lower testosterone levels were recently reported in males many years before RA onset but were predictive only of rheumatoid factor (RF)—negative disease. A preceding prospective study did not reveal androgenic-anabolic hormone association with risk of RA in men or women. This cohort study of males analyzed baseline serum levels of gonadal and adrenocortical steroids, luteinizing hormone, and prolactin in 18 pre-RA versus 72 matched non-RA control (CN) subjects. Findings in males were compared to those in female pre-RA and CN subjects in the same cohort, and sex differences were analyzed. Steroidal and hormonal levels, including total testosterone, were similar between male study groups. In females, mean (±SE) serum androstenedione (nmol/L) was slightly () lower in 36 pre-RA (6.7 ± 0.36) than 144 CN (7.6 ± 0.22). With the exception of 3 partial correlations of hormonal variables observed to differ between pre-RA versus CN subjects, the patterns were similar overall. However, partial correlations of hormonal variables differed frequently by sex, both within and between study groups. Alfonse T. Masi, Azeem A. Rehman, Robert T. Chatterton, Huaping Wang, Ned J. Goertzen, Kevin B. Elmore, and Jean C. Aldag Copyright © 2013 Alfonse T. Masi et al. All rights reserved. Rheumatoid Factor Positivity Is Associated with Increased Joint Destruction and Upregulation of Matrix Metalloproteinase 9 and Cathepsin K Gene Expression in the Peripheral Blood in Rheumatoid Arthritic Patients Treated with Methotrexate Thu, 14 Nov 2013 14:34:19 +0000 http://www.hindawi.com/journals/ijr/2013/457876/ We evaluated changes in gene expression of mTOR, p21, caspase-3, ULK1, TNFα, matrix metalloproteinase (MMP)-9, and cathepsin K in the whole blood of rheumatoid arthritic (RA) patients treated with methotrexate (MTX) in relation to their rheumatoid factor status, clinical, immunological, and radiological parameters, and therapeutic response after a 24-month follow-up. The study group consisted of 35 control subjects and 33 RA patients without previous history of MTX treatment. Gene expression was measured using real-time RT-PCR. Decreased disease activity in patients at the end of the study was associated with significant downregulation of TNFα expression. Downregulation of mTOR was observed in seronegative patients, while no significant changes in the expression of p21, ULK1, or caspase-3 were noted in any RA patients at the end of the study. The increase in erosion numbers observed in the seropositive patients at the end of the follow-up was accompanied by upregulation of MMP-9 and cathepsin K, while seronegative patients demonstrated an absence of significant changes in MMP-9 and cathepsin K expression and no increase in the erosion score. Our results suggest that increased expression of MMP-9 and cathepsin K genes in the peripheral blood might indicate higher bone tissue destruction activity in RA patients treated with methotrexate. The clinical study registration number is 0120.0810610. Elena V. Tchetina, Natalia V. Demidova, Dmitry E. Karateev, and Eugeny L. Nasonov Copyright © 2013 Elena V. Tchetina et al. All rights reserved. The Assessment of Disease Activity in Rheumatic Diseases Thu, 07 Nov 2013 09:49:37 +0000 http://www.hindawi.com/journals/ijr/2013/275691/ Thurayya Arayssi, Zahi Touma, Mandana Nikpour, and Lilian Ghandour Copyright © 2013 Thurayya Arayssi et al. All rights reserved. The Utility of Outcome Measures in Total Knee Replacement Surgery Thu, 31 Oct 2013 15:10:22 +0000 http://www.hindawi.com/journals/ijr/2013/506518/ Total knee replacement (TKR) is the mainstay of treatment for people with end-stage knee OA among suitably “fit” candidates. As a high cost, high volume procedure with a worldwide demand that continues to grow it has become increasingly popular to measure response to surgery. While the majority who undergo TKR report improvements in pain and function following surgery, a significant proportion of patients report dissatisfaction with surgery as a result of ongoing pain or poor function. Poor outcomes of TKR require care that imposes on already overburdened health systems. Accurate and meaningful capture and interpretation of outcome data are imperative for appropriate patient selection, informing those at risk, and for developing strategies to mitigate the risk of poor results and dissatisfaction. The ways in which TKR outcomes are captured and analysed, the level of follow-up, the types of outcome measures used, and the timing of their application vary considerably within the literature. With this in mind, we reviewed four of the most commonly used joint specific outcome measures in TKR. We report on the utility, strengths, and limitations of the Oxford knee score (OKS), knee injury and osteoarthritis outcome score (KOOS), Western Ontario and McMaster Universities osteoarthritis index (WOMAC), and knee society clinical rating system (KSS). Michelle M. Dowsey and Peter F. M. Choong Copyright © 2013 Michelle M. Dowsey and Peter F. M. Choong. All rights reserved. Long-Term Drug Survival of TNF Inhibitor Therapy in RA Patients: A Systematic Review of European National Drug Registers Wed, 30 Oct 2013 10:26:27 +0000 http://www.hindawi.com/journals/ijr/2013/764518/ Objective. The present systematic review of RA registry data was undertaken to analyse the time on treatment of licensed TNF inhibitors in patients with RA in Europe. Methods. English language European registry studies comparing TNF inhibitors were searched using MEDLINE, Embase, Cochrane, and WHO: ICTRP up to 16 April 2012 and proceedings of three selected conferences held between 2010 and 2012. Pooled analysis was performed to determine drug survival rates for each TNF inhibitor. Results. Sixteen studies met the inclusion criteria, of which 11 studies assessed biologic-naive patients and five studies included a mixed population of biologic-naive and biologic pretreated patients. The overall effectiveness of TNF inhibitors diminished with time, leading to decreased drug survival rates. Pooled drug survival rates after 60 months follow-up were 37% (infliximab), 48% (adalimumab), and 52% (etanercept). Further, in an observational study, when TNF inhibitors were used in combination with methotrexate, a longer drug survival was observed compared to TNF inhibitors alone. Conclusion. The findings of this systematic review indicated numerically lower drug discontinuation rates with etanercept than adalimumab, whereas infliximab had the highest rate. Further research is needed to understand the underlying mechanisms of treatment discontinuation with TNF inhibitors. Anamika Arora, Anadi Mahajan, Dean Spurden, Helen Boyd, and Duncan Porter Copyright © 2013 Anamika Arora et al. All rights reserved. Capability and Limitations of Recent Diagnostic Criteria for Autoimmune Pancreatitis Wed, 30 Oct 2013 08:28:50 +0000 http://www.hindawi.com/journals/ijr/2013/465428/ Because a diagnostic serological marker is unavailable, autoimmune pancreatitis (AIP) is diagnosed based on unique features. The diagnostic capabilities and potential limitations of four sets of diagnostic criteria for AIP (Japanese diagnostic criteria 2006 and 2011, Asian diagnostic criteria, and international consensus diagnostic criteria (ICDC)) were compared among 85 patients who were diagnosed AIP according to at least one of the four sets. AIP was diagnosed in 87%, 95%, 95%, and 95% of the patients according to the Japanese 2006, Asian, ICDC, and Japanese 2011 criteria, respectively. The ICDC can diagnose types 1 and 2 AIP independently and show high sensitivity for diagnosis of AIP. However, as the ICDC are rather complex, diagnostic criteria for AIP should perhaps be revised and tailored to each country based on the ICDC. Taku Tabata, Terumi Kamisawa, Sawako Kuruma, Kazuro Chiba, Susumu Iwasaki, Go Kuwata, Takashi Fujiwara, Hideto Egashira, Satomi Koizumi, Yuka Endo, Koichi Koizumi, Junko Fujiwara, Takeo Arakawa, and Kumiko Momma Copyright © 2013 Taku Tabata et al. All rights reserved. Monogenic Autoinflammatory Syndromes: State of the Art on Genetic, Clinical, and Therapeutic Issues Thu, 24 Oct 2013 17:19:51 +0000 http://www.hindawi.com/journals/ijr/2013/513782/ Monogenic autoinflammatory syndromes (MAISs) are caused by innate immune system dysregulation leading to aberrant inflammasome activation and episodes of fever and involvement of skin, serous membranes, eyes, joints, gastrointestinal tract, and nervous system, predominantly with a childhood onset. To date, there are twelve known MAISs: familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, familial cold urticaria syndrome, Muckle-Wells syndrome, CINCA syndrome, mevalonate kinase deficiency, NLRP12-associated autoinflammatory disorder, Blau syndrome, early-onset sarcoidosis, PAPA syndrome, Majeed syndrome, and deficiency of the interleukin-1 receptor antagonist. Each of these conditions may manifest itself with more or less severe inflammatory symptoms of variable duration and frequency, associated with findings of increased inflammatory parameters in laboratory investigation. The purpose of this paper is to describe the main genetic, clinical, and therapeutic aspects of MAISs and their most recent classification with the ultimate goal of increasing awareness of autoinflammation among various internal medicine specialists. Francesco Caso, Donato Rigante, Antonio Vitale, Orso Maria Lucherini, Luisa Costa, Mariangela Atteno, Adele Compagnone, Paolo Caso, Bruno Frediani, Mauro Galeazzi, Leonardo Punzi, and Luca Cantarini Copyright © 2013 Francesco Caso et al. All rights reserved. Comparison of the Systemic Lupus Erythematosus Activity Questionnaire and the Systemic Lupus Erythematosus Disease Activity Index in a Black Barbadian Population Thu, 24 Oct 2013 12:40:20 +0000 http://www.hindawi.com/journals/ijr/2013/875369/ In Barbados, use of the Systemic Lupus Erythematosus (SLE) Disease Activity Index (SLEDAI) is limited by the unavailability of serologic markers. The SLE Activity Questionnaire (SLAQ) excludes laboratory measurements and is therefore more accessible. Here, we investigate the agreement between the SLAQ, the SLEDAI, and the physician global assessment (PGA). A pilot of 32 participants completed the SLAQ and SLEDAI. The tools were compared (1) in their original format, (2) limited to common indices, and (3) limited to the same patient recall period. We compared the proportions of persons reporting disease activity and the concordance between calculated activity scores for SLAQ versus SLEDAI and for SLAQ versus PGA. Seventy-eight percent versus 59% of participants reported disease activity with the original SLEDAI versus SLAQ, respectively. The relationship was reversed to 22% versus 59% when the matched item tools were compared. Concordance was 0.62 (95% CI 0.42–0.81) between the original scores, 0.70 (0.57–0.83) when restricted by matched items, and 0.72 (0.59–0.84) when further restricted by recall period. Concordance between the SLAQ and PGA was 0.56 (0.32–0.80). Reversal of the disease activity percentage in the matched items comparison highlights the inadequacy of tools that exclude laboratory measurements and suggests that the subjective nature of SLAQ may contribute to over-reporting. Further work is needed to produce a robust disease activity tool apt for resource-constrained environments. Kim R. Quimby, Cindy Flower, Ian R. Hambleton, R. Clive Landis, and Anselm J. M. Hennis Copyright © 2013 Kim R. Quimby et al. All rights reserved. The Role of Klebsiella in Crohn’s Disease with a Potential for the Use of Antimicrobial Measures Thu, 10 Oct 2013 09:23:31 +0000 http://www.hindawi.com/journals/ijr/2013/610393/ There is a general consensus that Crohn’s disease (CD) develops as the result of immune-mediated tissue damage triggered by infections with intestinal microbial agents. Based on the results of existing microbiological, molecular, and immunological studies, Klebsiella microbe seems to have a key role in the initiation and perpetuation of the pathological damage involving the gut and joint tissues in patients with CD. Six different gastroenterology centres in the UK have reported elevated levels of antibodies to Klebsiella in CD patients. There is a relationship between high intake of starch-containing diet, enhanced growth of gut microbes, and the production of pullulanases by Klebsiella. It is proposed that eradication of these microbes by the use of antibiotics and low starch diet, in addition to the currently used treatment, could help in alleviating or halting the disease process in CD. Taha Rashid, Alan Ebringer, and Clyde Wilson Copyright © 2013 Taha Rashid et al. All rights reserved. Anti-CCP Antibodies Are Not Associated with Familial Mediterranean Fever in Childhood Mon, 09 Sep 2013 09:05:53 +0000 http://www.hindawi.com/journals/ijr/2013/498581/ Objective. Anticyclic citrullinated peptide antibodies (anti-CCP) testing is useful in the diagnosis of rheumatoid arthritis (RA) with high specificity. Arthritis is a very common clinical manifestation in children with familial Mediterranean fever (FMF). The aim of the study was to show the presence of anti-CCP antibodies in child individuals diagnosed with FMF. Material and Methods. The study groups comprised one hundred and twenty-six patients (126) diagnosed with FMF (female/male (): 66/60) and 50 healthy controls (female/male (): 25/25). Clinical and laboratory assessments of the FMF patients were performed during attack-free periods. Erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), fibrinogen, and anti-CCP antibody levels were measured. Results. Anti-CCP was negative in healthy controls and also in all FMF patients. There was not a significant difference in anti-CCP between the patient and the control groups. Our study has shown that anti-CCP was correlated moderately with age (; ), duration of illness (; ), and colchicine therapy (; ). Conclusion. Our data show that anti-CCP antibodies are not associated with FMF. Anti-CCP does not have a priority for identifying FMF arthritis from the other inflammatory arthritis. Hatice Onur, Hale Aral, Vefik Arica, Gamze Bercem, Murat Usta, and Özgur Kasapcopur Copyright © 2013 Hatice Onur et al. All rights reserved. Disease Activity Measures in Paediatric Rheumatic Diseases Sun, 08 Sep 2013 10:15:36 +0000 http://www.hindawi.com/journals/ijr/2013/715352/ Disease activity refers to potentially reversible aspects of a disease. Measurement of disease activity in paediatric rheumatic diseases is a critical component of patient care and clinical research. Disease activity measures are developed systematically, often involving consensus methods. To be useful, a disease activity measure must be feasible, valid, and interpretable. There are several challenges in quantifying disease activity in paediatric rheumatology; namely, the conditions are multidimensional, the level of activity must be valuated in the context of treatment being received, there is no gold standard for disease activity, and it is often difficult to incorporate the patient’s perspective of their disease activity. To date, core sets of response variables are defined for juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, and juvenile dermatomyositis, as well as definitions for improvement in response to therapy. Several specific absolute disease activity measures also exist for each condition. Further work is required to determine the optimal disease activity measures in paediatric rheumatology. Nadia J. Luca and Brian M. Feldman Copyright © 2013 Nadia J. Luca and Brian M. Feldman. All rights reserved. Circulating Levels of Soluble Receptor Activator of NF-κB Ligand and Matrix Metalloproteinase 3 (and Their Antagonists) in Asian Indian Patients with Ankylosing Spondylitis Sun, 01 Sep 2013 11:48:11 +0000 http://www.hindawi.com/journals/ijr/2013/814350/ Background. Bone loss in ankylosing spondylitis may be related to inflammation. Data from previous studies on circulating levels of sRANKL, OPG, MMP3, and TIMP is inconsistent; thus this study is planned to look at this aspect in Asian Indian patients. Methods. Cross-sectional study included patients with ankylosing spondylitis and age- and gender-similar controls. Serum levels of sRANKL, OPG, MMP-3, and TIMP-1 were measured by ELISA. Results. Included 85 patients (M : F = 82 : 3) having mean age (±SD) years and disease duration years. BASDAI, BASFI, BASMI, and ESR were , , and respectively. Patients had higher mean (±SD) OPG level (,  pg/mL, ). However, there was no difference in sRANKL (, , ). Serum MMP-3 (,  ng/mL, ) and TIMP-1 (,  ng/mL, ) levels were higher in patients; however, there was no difference in MMP-3/TIMP-1 ratio. Conclusion. Circulating levels of OPG were higher; however, there was no difference in sRANKL in Asian Indian ankylosing spondylitis patients. Although both MMP-3 and TIMP-1 were raised, their ratio was not different from that of controls. Varun Dhir, Rajni Srivastava, and Amita Aggarwal Copyright © 2013 Varun Dhir et al. All rights reserved. Detailed Joint Region Analysis of the 7-Joint Ultrasound Score: Evaluation of an Arthritis Patient Cohort over One Year Mon, 12 Aug 2013 17:26:21 +0000 http://www.hindawi.com/journals/ijr/2013/493848/ Objective. The main objective of this study was to evaluate the 7-joint ultrasound (US7) score by detailed joint region analysis of an arthritis patient cohort. Methods. The US7 score examines the clinically most affected wrist, MCP and PIP II, III, MTP II, and V joints for synovitis, tenosynovitis/paratenonitis, and erosions. Forty-five patients with rheumatoid arthritis (RA) (84.4%) and spondyloarthritis with polyarticular peripheral arthritis (PsA 13.3%; AS 2.2%) with a median disease duration of 6.5 yrs (range 7.5 mths–47.6 yrs) were included and examined at baseline and 3, 6, and 12 months after starting or changing therapy (DMARD/biologic). In this study, detailed US7 score joint region analysis was firstly performed. Results. The joint region analysis performed at baseline disclosed synovitis in 95.6% of affected wrists in the dorsal aspect by greyscale (GS) US where Grade 2 (moderate) was most often (48.9%) detected. Palmar wrist regions presented Grade 1 (minor) capsule elevation in 40% and Grade 2 (moderate synovitis) in 37.8%. Tenosynovitis of the extensor carpi ulnaris (ECU) tendon was found in 40%, with PD activity in 6.6%. Most of the erosions in MCP II were detected in the radial (68.9%), followed by the dorsal (48.9%) and palmar (44.4%) aspects. In MTP V, erosions were seen in 75.6% from lateral. Conclusions. Synovitis in GSUS was more often detected in the wrist in the dorsal than in the palmar aspect. ECU tendon involvement was frequent. Most erosions were found in the lateral scan of MTP V and the medial (radial) scan of MCP II. S. Ohrndorf, B. Halbauer, P. Martus, B. Reiche, T. M. Backhaus, G. R. Burmester, and M. Backhaus Copyright © 2013 S. Ohrndorf et al. All rights reserved. Serum Immunoglobulin Free Light Chain Assessment in IgG4-Related Disease Wed, 26 Jun 2013 12:55:40 +0000 http://www.hindawi.com/journals/ijr/2013/426759/ Immunoglobulin free light chains are produced in excess during normal antibody synthesis. Their evaluation is commonly used in case of a monoclonal gammopathy. In polyclonal hypergammaglobulinemia related to the Sjögren syndrome or systemic lupus, erythematosus serum free light chain levels are increased and could correlate with disease activity. We show here that the κ () and λ () free light chains and the κ : λ ratio () are increased in sixteen patients with IgG4-related disease when compared to healthy controls. The increase of κ and λ free light chains probably reflects the marked polyclonal B cell activation of the disease. We could not assess in this small cohort of patients a significative correlation of serum free light chain levels and disease activity or extension. Aurélie Grados, Mikael Ebbo, José Boucraut, Frédéric Vély, Pierre Aucouturier, Aude Rigolet, Benjamin Terrier, David Saadoun, Pascale Ghillani-Dalbin, Nathalie Costedoat-Chalumeau, Jean Robert Harlé, and Nicolas Schleinitz Copyright © 2013 Aurélie Grados et al. All rights reserved. The Characteristics and Significance of Locally Infiltrating B Cells in Lupus Nephritis and Their Association with Local BAFF Expression Wed, 12 Jun 2013 13:03:07 +0000 http://www.hindawi.com/journals/ijr/2013/954292/ Introduction. Dysfunction of the B lymphocyte is considered to be involved in the pathogenesis of lupus nephritis (LN). Intrarenal B cells have been found in several forms of inflammatory kidney disease. B-cell activating factor (BAFF) regulates B lymphocyte proliferation and survival, and contributes to human autoimmune disease. Their role in renal inflammation is not well defined. Methods. Clinical parameters and renal biopsies from 62 LN patients were prospectively analyzed. We performed standard immunohistochemistry on serial paraffin tissue sections using monoclonal antibodies to CD20 and BAFF to investigate the characteristics and significance of locally infiltrating B cells and local BAFF expression in patients with LN. Results. Intrarenal B cells and/or BAFF were mainly distributed in the renal interstitium. Compared to the LN-non-B-cell/BAFF expression group, proteinuria (g/24 hour), blood urea nitrogen, serum creatinine levels, LN renal activity, and chronicity indices, were all significantly greater in the LN-B-cell/BAFF expression groups. The expression of BAFF was strongly associated with the quantity of B-cell infiltrate in the interstitium. Conclusion. As BAFF expression was strongly associated with B-cell infiltration, we hypothesize that altered B-cell differentiation and tolerance induced by excess BAFF may be central to the pathogenesis of LN. Chuan-Yin Sun, Yan Shen, Xiao-Wei Chen, Yu-Cheng Yan, Feng-Xia Wu, Ming Dai, Ting Li, and Cheng-De Yang Copyright © 2013 Chuan-Yin Sun et al. All rights reserved. Possible Involvement of Foxp3+ Regulatory T Cells in the Development of Immune-Mediated Pancreatitis in MRL/Mp Mice Treated with Polyinosinic:Polycytidylic Acid Mon, 27 May 2013 08:09:49 +0000 http://www.hindawi.com/journals/ijr/2013/367325/ Objectives. This study was conducted to clarify whether or not Tregs are involved in the development of immune-mediated pancreatitis in MRL/Mp mice as an AIP (autoimmune pancreatitis) model, in order to understand more clearly the pathogenic mechanism of AIP. Methods. We compared the immunohistochemical features of pancreatic forkhead box P3 (Foxp3) in the administration of poly I:C in MRL/Mp mice and two types of control mice (BALB/c and C57BL/6). As a contrast, we analyzed three mouse models of pancreatitis without autoimmune mechanism (Cerulein-, Ligation-, and Ligation + Cerulein-treated mice). After staining these specimens, we compared the ratios of Foxp3-positive cells to infiltrated mononuclear cells (Foxp3/Mono). Results. Our immunohistochemical study of Foxp3 revealed that the infiltration of Foxp3-positive cells increased in poly I:C-treated MRL/Mp mice. The histopathological score of pancreatitis showed no difference among poly I:C-treated MRL/Mp, Ligation-, and Ligation + Cerulein-treated mice; however, the Foxp3/Mono ratio in poly I:C-treated MRL/Mp mice was significantly increased compared with Ligation- and Ligation + Cerulein-treated mice. Conclusions. MRL/Mp mice treated with poly I:C showed early development of pancreatitis with abundant infiltration of Foxp3-positive cells. There may be a possibility that Tregs are involved in the development of pancreatitis in these mice. Masanori Koyabu, Kazushige Uchida, Yutaku Sakaguchi, Norimasa Fukata, Takeo Kusuda, Hideaki Miyoshi, Katsunori Yoshida, Kimi Sumimoto, Toshiyuki Mitsuyama, Toshiro Fukui, Akiyoshi Nishio, and Kazuichi Okazaki Copyright © 2013 Masanori Koyabu et al. All rights reserved. Type 1 Autoimmune Pancreatitis Can Transform into Chronic Pancreatitis: A Long-Term Follow-Up Study of 73 Japanese Patients Thu, 16 May 2013 08:18:00 +0000 http://www.hindawi.com/journals/ijr/2013/272595/ Some patients with autoimmune pancreatitis (AIP) form pancreatic stones suggestive of transformation into chronic pancreatitis (CP). The present study examined the underlying risk factors and mechanism of AIP progression to confirmed CP. We compared the clinical and laboratory parameters of subjects who progressed to confirmed CP with those of the subjucts who did not in a cohort of 73 type 1 AIP patients. A total of 16 (22%) AIP patients progressed to CP. Univariate analysis revealed that relapse was significantly more frequent in the progression group, and multivariate analysis indicated that pancreatic head swelling (OR 12.7, ) and nonnarrowing of the main pancreatic duct in the pancreatic body (OR 12.6, ) were significant independent risk factors for progression to CP. Kaplan-Meier testing showed that the progression rate to CP was approximately 10% at 3 years and 30% at 10 years in total AIP patients and 30% at 3 years and 60% at 10 years in subjects with both risk factors. AIP with pancreatic head swelling and a history of relapse may cause pancreatic juice stagnation and nonnarrowing of the main pancreatic duct in the pancreatic body, which can progress to advanced stage chronic pancreatitis. Masahiro Maruyama, Norikazu Arakura, Yayoi Ozaki, Takayuki Watanabe, Tetsuya Ito, Suguru Yoneda, Masafumi Maruyama, Takashi Muraki, Hideaki Hamano, Akihiro Matsumoto, and Shigeyuki Kawa Copyright © 2013 Masahiro Maruyama et al. All rights reserved. Design of the Tocilizumab in Giant Cell Arteritis Trial Sun, 07 Apr 2013 15:08:59 +0000 http://www.hindawi.com/journals/ijr/2013/912562/ Overview. The GiACTA trial is a multicenter, randomized, double-blind, and placebo-controlled study designed to test the ability of tocilizumab (TCZ), an interleukin (IL)-6 receptor antagonist, to maintain disease remission in patients with giant cell arteritis (GCA). Design. Approximately 100 centers will enroll 250 patients with active disease. The trial consists of a 52-week blinded treatment phase followed by 104 weeks of open-label extension. Patients will be randomized into one of four groups. Group A (TCZ 162 mg weekly plus a 6-month prednisone-taper); group B (TCZ 162 mg every other week plus a 6-month prednisone-taper); group C (placebo plus a 6-month prednisone-taper); and group D (placebo plus a 12-month prednisone taper). We hypothesize that patients assigned to TCZ in addition to a 6-month prednisone course are more likely to achieve the primary efficacy endpoint of sustained remission (SR) at 52 weeks compared with those assigned to a 6-month prednisone course alone, thus potentially minimizing the long-term adverse effects of corticosteroids. Conclusion. GiACTA will test the hypothesis that interference with IL-6 signaling exerts a beneficial effect on patients with GCA. The objective of this paper is to describe the design of the trial and address major issues related to its development. Sebastian H. Unizony, Bhaskar Dasgupta, Elena Fisheleva, Lucy Rowell, Georg Schett, Robert Spiera, Jochen Zwerina, Olivier Harari, and John H. Stone Copyright © 2013 Sebastian H. Unizony et al. All rights reserved. Adverse Event Burden, Resource Use, and Costs Associated with Immunosuppressant Medications for the Treatment of Systemic Lupus Erythematosus: A Systematic Literature Review Wed, 03 Apr 2013 10:16:39 +0000 http://www.hindawi.com/journals/ijr/2013/347520/ This paper assessed the burden of adverse events (AEs) associated with azathioprine (AZA), cyclophosphamide (CYC), mycophenolate mofetil (MMF), methotrexate (MTX), and cyclosporine (CsA) in patients with systemic lupus erythematosus (SLE). Thirty-eight publications were included. Incidence of AEs ranged from 42.8% to 97.3%. Common AEs included infections (2.4–77%), gastrointestinal AEs (3.2–66.7%), and amenorrhea and/or ovarian complications (0–71%). More hematological cytopenias were associated with AZA (14 episodes) than MMF (2 episodes). CYC was associated with more infections than MMF (40–77% versus 12.5–32%, resp.) or AZA (17–77% versus 11–29%, resp.). Rates of hospitalized infections were similar between MMF and AZA patients, but higher for those taking CYC. There were more gynecological toxicities with CYC than MMF (32–36% versus 3.6–6%, resp.) or AZA (32–71% versus 8–18%, resp.). Discontinuation rates due to AEs were 0–44.4% across these medications. In summary, the incidence of AEs associated with SLE immunosuppressants was consistently high as reported in the literature; discontinuations due to these AEs were similar across treatments. Studies on the economic impact of these AEs were sparse and warrant further study. This paper highlights the need for more treatment options with better safety profiles. A. Oglesby, A. J. Shaul, T. Pokora, C. Paramore, L. Cragin, G. Dennis, S. Narayanan, and A. Weinstein Copyright © 2013 A. Oglesby et al. All rights reserved. Validation of a Prediction Rule for the Diagnosis of Rheumatoid Arthritis in Patients with Recent Onset Undifferentiated Arthritis Thu, 28 Feb 2013 18:11:43 +0000 http://www.hindawi.com/journals/ijr/2013/548502/ Objectives. To validate van der Helm-van Mil score (vHvM) and new ACR/EULAR criteria for the diagnosis of rheumatoid arthritis (RA) in patients with undifferentiated arthritis (UA). Patients and Methods. Adult patients with UA (swelling ≥2 joints of less than 6 months duration, without diagnosis, and never treated with disease modifying drugs). Results. Ninety-one patients were included. Mean age: 55.6 years (SD: 17.4), 74% females. Median symptoms duration was 2 months (IR: 1–4 months). Mean van der Helm-van Mil score was 6.9 (SD: 2). After a mean followup of 6.2 months (SD: 6), 40.7% patients fulfilled ACR 1987 RA classification criteria, 28.6% fulfilled other diagnostic criteria, and 31% remained as UA. Receiver operator characteristic curve's (ROC's) area under the curve (AUC) for the vHvM score for diagnosis of RA was 0.83. A cutoff value of 6.94 showed sensitivity of 81% and 79.7% specificity. For the new ACR/EULAR criteria, the ROC AUC was 0.93, and a value equal to or greater than 6 showed 86.5% sensitivity and 87% specificity. Conclusion. van der Helm-van Mil prediction score and the new ACR/EULAR criteria proved to be valuable for the diagnosis of RA in patients with early UA. Zaida Bedran, Cristian Quiroz, Javier Rosa, Luis J. Catoggio, and Enrique R. Soriano Copyright © 2013 Zaida Bedran et al. All rights reserved. Health Care Costs Associated with Ankylosing Spondylitis in Turkey: An Analysis from Nationwide Real-World Data Tue, 19 Feb 2013 12:55:51 +0000 http://www.hindawi.com/journals/ijr/2013/139608/ Objectives. To explore health care costs associated with ankylosing spondylitis (AS) in Turkey. Methods. Research-identified data from a system that processes claims for all Turkish health insurance funds were analyzed. Adult prevalent and incident AS patients with two AS visits at least 60 days apart, identified between June 1, 2010 and December 31, 2010, with at least 1 year of continuous health plan enrollment for the baseline and follow-up years were included in the study. Pharmacy, outpatient, and inpatient claims were compiled over the study period for the selected patients. Generalized linear models were used to estimate the expected annual costs, controlling for baseline demographic and clinical characteristics. Results. A total of 2.986 patients were identified, of which 603 were incident cases and 2.383 prevalent cases. The mean ages were 39 and 41 years, respectively, and 44% and 38% were women for incident and prevalent cases. Prevalent patients had higher comorbidity scores (5.01 versus 2.24, ) and were more likely to be prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) (77% versus 72%, ) or biologics (35% versus 8%, ) relative to incident patients. Seventy-seven percent of prevalent patients were prescribed NSAIDs, followed by biologic and disease-modifying antirheumatic drugs (DMARDs). Total annual medical costs for incident AS patients were €2.253 and €4.233 for prevalent patients. Pharmacy costs accounted for a significant portion of total costs (88% for prevalent patient, 77% for incident patient), followed by physician office visit costs. Prior comorbidities and treatment type also significantly contributed to overall costs. Conclusion. Annual expenditures for AS patients in Turkey were comparable relative to European countries. Pharmaceutical expenditures cover a significant portion of the overall costs. Comparative effectiveness studies are necessary to further decrease health care costs of AS treatment. Onur Baser, Abdulkadir Burkan, Erdem Baser, Rasim Koselerli, Emre Ertugay, and Akif Altinbas Copyright © 2013 Onur Baser et al. All rights reserved. IgG4-Related Disease Wed, 16 Jan 2013 07:51:59 +0000 http://www.hindawi.com/journals/ijr/2013/532612/ John H. Stone, John K. C. Chan, Vikram Deshpande, Kazuichi Okazaki, Hisanori Umehara, and Yoh Zen Copyright © 2013 John H. Stone et al. All rights reserved. Changes of CD4+ CD25+ Regulatory T Cells, FoxP3 in Adjuvant Arthritis Rats with Damage of Pulmonary Function and Effects of Tripterygium Glycosides Tablet Thu, 27 Dec 2012 15:06:56 +0000 http://www.hindawi.com/journals/ijr/2012/348450/ Objective. To observe the effects of tripterygium glycosides tablet (TPT) on swelling degree, arthritis index (AI), pulmonary function, cytokines, the expression of regulatory T cells (Treg), and Foxp3 in rats of adjuvant arthritis. Methods. Rats were averagely divided into normal control (NC) group, model control (MC) group, methotrexate (MTX) group, and tripterygium glycosides tablet (TPT) group. Except for the rats of normal group, the others were intracutaneously injected with 0.1 mL of Freund’s complete adjuvant in the right hindlimb. NC group and MC group were treated with physiological saline. MTX group and TPT group were treated with MTX, TPT, respectively. Results. The levels of swelling degree, AI, the alveolar inflammation integral, TNF alpha (TNF-), and endothelium-1 (ET-1 ) in MC group were significantly increased (), and the levels of forced vital capacity (FVC), 25% vital capacity of the peak expiratory flow (FEF25), 50% vital capacity of the peak expiratory flow (FEF50), 75% vital capacity of the peak expiratory flow (FEF75), maximum midexpiratory flow (MMF), peak expiratory flow (PEF), interleukin-10 (IL-10), CD4+ CD25+ Treg, and Foxp3 were decreased (). The scores of alveolitis and ET-1 were decreased with treatment of TPT. The levels of FVC, FEF25, FEF50, FEF75, MMF, PEF, IL-10, and CD4+ CD25+ Treg in peripheral blood were increased. The expressions of Foxp3 protein and mRNA in lung tissue were also increased in TPT group. Conclusions. The paw swelling can be inhibited by TPT, and the inflammatory response in lung tissue was also decreased, which is a significant improvement in pulmonary function. The mechanism is probably associated with upregulating the expression of IL-10, Foxp3, and downregulating the level of TNF-. Wan Lei and Liu Jian Copyright © 2012 Wan Lei and Liu Jian. All rights reserved. Measuring Disease Activity in Psoriatic Arthritis Tue, 25 Dec 2012 08:50:50 +0000 http://www.hindawi.com/journals/ijr/2012/839425/ Over the past decade, the assessment of the disease activity in psoriatic arthritis (PsA) has rapidly evolved in view of the need for valid, feasible, and reliable outcome measures that can be ideally employed in longitudinal cohorts, clinical trials, and clinical practice as well as the growing paradigm of tight disease control and treating to target in the management of PsA. This paper reviews the currently available measures used in the assessment of the disease activity in PsA. The composite measures for PsA that are under development are also discussed. Priscilla C. H. Wong, Ying-Ying Leung, Edmund K. Li, and Lai-Shan Tam Copyright © 2012 Priscilla C. H. Wong et al. All rights reserved.