International Journal of Rheumatology https://www.hindawi.com The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. The CEDAR Study: A Longitudinal Study of the Clinical Effects of Conventional DMARDs and Biologic DMARDs in Australian Rheumatology Practice Tue, 23 May 2017 06:22:07 +0000 http://www.hindawi.com/journals/ijr/2017/1201450/ Objectives. To observe the choices of conventional disease modifying antirheumatic drugs (cDMARDs) and biologic DMARDs (bDMARDs) in the management of rheumatoid arthritis (RA) in Australian routine clinical practice, to assess treatment survival and determine the effect of cDMARDs/bDMARDs on disease activity. Methods. Routinely collected, deidentified clinical data was sourced from 20 Australian rheumatology practices. RA patients aged ≥18 years, who had received cDMARDs/bDMARDs and a recorded subsequent visit, were included. A linear mixed model was used to determine the change over time and the percentage reduction in disease activity was summarized. Results. 12,526 RA patients were included: 72% females, mean age 62 years. cDMARDs and bDMARDs were used in 92% and 30% of patients, respectively. The most commonly prescribed cDMARD was methotrexate (76% patients); median time to stopping treatment was 337 months [95% CI: 279–ND]. Etanercept was the most commonly prescribed bDMARD (12% patients); median time to stopping treatment was 79 months [95% CI: 57–93]. Of 5,341 patients with a first change in medication (cDMARD or bDMARD), 87% had therapy escalation and 13% deescalation. Reduction in DAS28-ESR, 6-month post-DMARDs initiation ranged from 3%, adalimumab, to 14%, leflunomide and tocilizumab. Conclusions. In this large Australian cohort of unselected community RA patients, the choices of cDMARDs/bDMARDs are aligned with current international guidelines. Lynden Roberts, Kathleen Tymms, Julien de Jager, Geoffrey Littlejohn, Hedley Griffiths, Dave Nicholls, Paul Bird, Jennifer Young, Julie Hill, and Jane Zochling Copyright © 2017 Lynden Roberts et al. All rights reserved. The Nonradiographic Axial Spondyloarthritis, the Radiographic Axial Spondyloarthritis, and Ankylosing Spondylitis: The Tangled Skein of Rheumatology Sun, 07 May 2017 00:00:00 +0000 http://www.hindawi.com/journals/ijr/2017/1824794/ Since 1984 the diagnosis of ankylosing spondylitis (AS) has been based upon the modified New York (mNY) criteria with mandatory presence of radiographic sacroiliitis, without which the diagnosis is not tenable. However, it may take years or decades for radiographic sacroiliitis to develop delaying the diagnosis for long periods. It did not matter in the past because no effective treatment was available. However, with the availability of a highly effective treatment, namely, tumour necrosis factor-α inhibitors (TNFi), the issue of early diagnosis of AS acquired an urgency. The Assessment of SpondyloArthritis International Society (ASAS) classification criteria published in 2009 was a significant step towards this goal. These criteria described an early stage of the disease where sacroiliitis was demonstrable only on MRI but not on standard radiograph. Therefore, this stage of the disease was labelled “nonradiographic axial SpA” (nr-axSpA). But questions have been raised if, in search of early diagnosis, specificity was compromised. The Federal Drug Administration (FDA, USA) withheld approval for the use of TNFi in patients with nr-axSpA because of issues related to the specificity of these criteria. This review attempts to clarify some of these aspects of the nr-axSpA-AS relationship and also tries to answer the question whether ASAS classifiable radiographic axial spondyloarthritis (r-axSpA) term can be interchangeably used with the term AS. Anand N. Malaviya, Roopa Rawat, Neha Agrawal, and Nilesh S. Patil Copyright © 2017 Anand N. Malaviya et al. All rights reserved. Tofacitinib versus Biologic Treatments in Moderate-to-Severe Rheumatoid Arthritis Patients Who Have Had an Inadequate Response to Nonbiologic DMARDs: Systematic Literature Review and Network Meta-Analysis Thu, 09 Mar 2017 00:00:00 +0000 http://www.hindawi.com/journals/ijr/2017/8417249/ Objective. To compare the efficacy and tolerability of tofacitinib, an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), as monotherapy and combined with disease-modifying antirheumatic drugs (DMARDs) versus biological DMARDs (bDMARDs) and other novel DMARDs for second-line moderate-to-severe rheumatoid arthritis (RA) patients by means of a systematic literature review (SLR) and network meta-analysis (NMA). Methods. MEDLINE®, EMBASE®, and Cochrane Central Register of Controlled Trials were searched to identify randomized clinical trials (RCTs) published between 1990 and March 2015. Efficacy data based on American College of Rheumatology (ACR) response criteria, improvements in the Health Assessment Questionnaire Disability Index (HAQ-DI) at 6 months, and discontinuation rates due to adverse events were analyzed by means of Bayesian NMAs. Results. 45 RCTs were identified, the majority of which demonstrated a low risk of bias. Tofacitinib 5 mg twice daily (BID) and 10 mg BID monotherapy exhibited comparable efficacy and discontinuation rates due to adverse events versus other monotherapies. Tofacitinib 5 mg BID and 10 mg BID + DMARDs or methotrexate (MTX) were mostly comparable to other combination therapies in terms of efficacy and discontinuation due to adverse events. Conclusion. In most cases, tofacitinib had similar efficacy and discontinuation rates due to adverse events compared to biologic DMARDs. Evelien Bergrath, Robert A. Gerber, David Gruben, Tatjana Lukic, Charles Makin, and Gene Wallenstein Copyright © 2017 Evelien Bergrath et al. All rights reserved. Interobserver Agreement in Magnetic Resonance of the Sacroiliac Joints in Patients with Spondyloarthritis Mon, 13 Feb 2017 00:00:00 +0000 http://www.hindawi.com/journals/ijr/2017/3143069/ Background. Clinical, laboratory, and radiologic parameters are used for diagnosis and classification of spondyloarthritis (SpA). Magnetic resonance imaging (MRI) of sacroiliac (SI) joints is being increasingly used to detect early sacroiliitis. We decided to evaluate the interobserver agreement in MRI findings of SI joints of SpA patients between a local radiologist, a rheumatologist, and an expert radiologist in musculoskeletal diseases. Methods. 66 MRI images of the SI joints of patients with established diagnosis of SpA were evaluated. Agreement was expressed in Cohen’s kappa. Results. Interobserver agreement between a local radiologist and an expert radiologist was fair (). Only acute findings showed a moderate agreement (), while chronic findings revealed 76.5% of disagreement (). A fair agreement was observed in acute findings () as well as chronic findings () between a local radiologist and a rheumatologist. There was a substantial agreement between an expert radiologist and a rheumatologist (). In acute findings, a 100% agreement was achieved. Also chronic and acute plus chronic findings showed high levels of agreement and 0.62, resp.). Conclusions. Our study shows that rheumatologists may have similar MRI interpretations of SI joints in SpA patients as an expert radiologist. Juan C. Rueda, Sofia Arias-Correal, Andres Y. Vasquez, Enrique Calvo, Paola Peña, Marlon Porras, Jose-Ignacio Angarita, Eugenia-Lucia Saldarriaga, Ana M. Santos, and John Londono Copyright © 2017 Juan C. Rueda et al. All rights reserved. Hard Physical Work Intensifies the Occupational Consequence of Physician-Diagnosed Back Disorder: Prospective Cohort Study with Register Follow-Up among 10,000 Workers Tue, 31 Jan 2017 00:00:00 +0000 http://www.hindawi.com/journals/ijr/2017/1037051/ While musculoskeletal pain is common in the population, less is known about its labor market consequences in relation to physical activity at work. This study investigates whether hard physical work aggravates the consequences of back disorder. Using Cox regression analyses, we estimated the joint association of physical activity at work and physician-diagnosed back disorder in 2010 with the risk of register-based long-term sickness absence (LTSA) of at least 6 consecutive weeks during 2011-2012 among 9,544 employees from the general working population (Danish Work Environment Cohort Study). Control variables were age, gender, psychosocial work environment, smoking, leisure physical activity, BMI, depression, and mental health. At baseline, 19.4% experienced high low-back pain intensity (≥5, 0–9 scale) and 15.2% had diagnosed back disorder. While high pain intensity was a general predictor for LTSA, physician-diagnosed back disorder was a stronger predictor among those with hard physical work (HR 2.23; 95% CI 1.68–2.96) compared with light work (HR 1.40; 95% CI 1.09–1.80). Similarly, physician-diagnosed back disorder with simultaneous high pain intensity predicted LTSA to a greater extent among those with hard physical work. In conclusion, the occupational consequence of physician-diagnosed back disorder on LTSA is greater among employees with hard physical work. Emil Sundstrup and Lars Louis Andersen Copyright © 2017 Emil Sundstrup and Lars Louis Andersen. All rights reserved. Isolated Ro52 Antibodies as Immunological Marker of a Mild Phenotype of Undifferentiated Connective Tissue Diseases Sun, 22 Jan 2017 00:00:00 +0000 http://www.hindawi.com/journals/ijr/2017/3076017/ The term undifferentiated connective tissue disease (UCTD) is used to describe undiagnosed patients that do not fulfill classification criteria for definite connective tissue disease (Systemic Lupus, Systemic Sclerosis, Sjögren Syndrome, and Dermatomyositis/Polymyositis). It is important to find serological markers as predictors of the evolution or severity of these diseases. The objective of this retrospective study was to investigate if there was a milder subgroup of UCTD with a special clinical profile consisting only in the presence of anti-Ro52 autoantibodies. Immunological and clinical records of 62 patients attending the hospital during 30 months were studied. Results showed a target population formed by mostly women, aged between 40 and 80 years at the moment of the study, with a registered age of onset between 40 and 60 years. Speckled pattern was the most frequent pattern found by indirect immunofluorescence. Given the obtained results and keeping in mind possible limitations because of sample size, isolated positive anti-Ro52 autoantibodies seem to lead to a benign effect in terms of evolution of the disease. As a future objective, the follow-up of these patients should be necessary to investigate new clinical symptoms, serological markers, or development of a definite connective tissue disease over time. Ana Alonso-Larruga, Sagrario Bustabad, José Antonio Navarro-Gonzálvez, Beatriz Rodríguez-Lozano, Andrés Franco, and Yvelise Barrios Copyright © 2017 Ana Alonso-Larruga et al. All rights reserved. Physicians’ Perspectives on the Diagnosis and Treatment of Chronic Nonbacterial Osteomyelitis Tue, 10 Jan 2017 00:00:00 +0000 http://www.hindawi.com/journals/ijr/2017/7694942/ Background/Purpose. Understanding the practices of pediatric rheumatologists in diagnosing and treating chronic nonbacterial osteomyelitis (CNO) can provide important information to guide the development of consensus treatment plans. The objectives of this study were to determine physicians’ approaches to (1) diagnosing and monitoring CNO, (2) ordering a bone biopsy, and (3) making treatment decisions. Methods. A survey was distributed among members of the Childhood Arthritis and Rheumatology Research Alliance using a web-based questionnaire. Results. 121 of 277 (41%) attending physician members completed the survey. Plain radiographs (89%) were most commonly used followed by regional MRI (78%), bone scintigraphy (43%), and whole-body MRI (36%). The top three reasons for performing a biopsy were constitutional findings (66%), unifocal bone lesions (64%), and nocturnal bone pain (45%). Nearly all responders (95%) prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) as initial therapy. For patients who failed NSAID treatment, methotrexate (67%), tumor necrosis factor inhibitors (65%), and bisphosphonates (46%) were the next most commonly used treatments. The presence of a spinal lesion increased the use of bisphosphonate treatment. Conclusion. The diagnostic approach and disease activity monitoring for CNO varied among surveyed physicians. Our survey findings provided important background for the development of consensus treatment plans for CNO. Yongdong Zhao, Fatma Dedeoglu, Polly J. Ferguson, Sivia K. Lapidus, Ronald M. Laxer, Miranda C. Bradford, and Suzanne C. Li Copyright © 2017 Yongdong Zhao et al. All rights reserved. Validation of Administrative Osteoarthritis Diagnosis Using a Clinical and Radiological Population-Based Cohort Thu, 29 Dec 2016 14:46:32 +0000 http://www.hindawi.com/journals/ijr/2016/6475318/ Objectives. The validity of administrative osteoarthritis (OA) diagnosis in British Columbia, Canada, was examined against X-rays, magnetic resonance imaging (MRI), self-report, and the American College of Rheumatology criteria. Methods. During 2002–2005, 171 randomly selected subjects with knee pain aged 40–79 years underwent clinical assessment for OA in the knee, hip, and hands. Their administrative health records were linked during 1991–2004, in which OA was defined in two ways: (AOA1) at least one physician’s diagnosis or hospital admission and (AOA2) at least two physician’s diagnoses in two years or one hospital admission. Sensitivity, specificity, and predictive values were compared using four reference standards. Results. The mean age was 59 years and 51% were men. The proportion of OA varied from 56.3 to 89.7% among men and 77.4 to 96.4% among women according to reference standards. Sensitivity and specificity varied from 21 to 57% and 75 to 100%, respectively, and PPVs varied from 82 to 100%. For MRI assessment, the PPV of AOA2 was 100%. Higher sensitivity was observed in AOA1 than AOA2 and the reverse was true for specificity and PPV. Conclusions. The validity of administrative OA in British Columbia varied due to case definitions and reference standards. AOA2 is more suitable for identifying OA cases for research using this Canadian database. M. Mushfiqur Rahman, Jacek A. Kopec, Charlie H. Goldsmith, Aslam H. Anis, and Jolanda Cibere Copyright © 2016 M. Mushfiqur Rahman et al. All rights reserved. Corrigendum to “An Insight into Methods and Practices in Hip Arthroplasty in Patients with Rheumatoid Arthritis” Tue, 27 Dec 2016 12:05:45 +0000 http://www.hindawi.com/journals/ijr/2016/1741420/ Mohammad Saeed Mosleh-shirazi, Mazin Ibrahim, Philip Pastides, Wasim Khan, Habib Rahman, and Leila Jahangiri Copyright © 2016 Mohammad Saeed Mosleh-shirazi et al. All rights reserved. Immune Mediators in Osteoarthritis: Infrapatellar Fat Pad-Infiltrating CD8+ T Cells Are Increased in Osteoarthritic Patients with Higher Clinical Radiographic Grading Wed, 14 Dec 2016 14:31:51 +0000 http://www.hindawi.com/journals/ijr/2016/9525724/ Osteoarthritis is a condition of joint failure characterized by many pathologic changes of joint-surrounding tissues. Many evidences suggest the role of both innate and adaptive immunity that interplay, resulting either in initiation or in progression of osteoarthritis. Adaptive immune cells, in particular T cells, have been demonstrated to play a role in the development of OA in animal models. However, the underlying mechanism is yet unclear. Our aim was to correlate the frequency and phenotype of tissue-infiltrating T cells in the synovial tissue and infrapatellar fat pad with radiographic grading. Our results show that CD8+ T cells are increased in osteoarthritic patients with higher radiographic grading. When peripheral blood CD8+ T cells were examined, we show that CD8+ T cells possess a significantly higher level of activation than its CD4+ T cell counterpart (). Our results suggest a role for CD8+ T cells and recruitment of these activated circulating peripheral blood CD8+ T cells to the knee triggering local inflammation within the knee joint. Jirun Apinun, Panjana Sengprasert, Pongsak Yuktanandana, Srihatach Ngarmukos, Aree Tanavalee, and Rangsima Reantragoon Copyright © 2016 Jirun Apinun et al. All rights reserved. Serum Amyloid A Level in Egyptian Children with Familial Mediterranean Fever Tue, 13 Dec 2016 08:52:14 +0000 http://www.hindawi.com/journals/ijr/2016/7354018/ Background and Objectives. SAA is an acute-phase reactant detected during an FMF attack or other inflammatory conditions. High SAA levels may increase the risk of amyloidosis. The aim of the study is to measure the serum amyloid A (SAA) level in a group of Egyptian children with familial Mediterranean fever (FMF) and study its various correlates, if any. Methods. The study enrolled seventy-one children with FMF. Results. SAA level was high in 78.9% of the studied patients with a mean of  mg/L, and CRP was positive in 31% of patients. There was no significant releation between SAA level and any demographic or clinical manifestation. High SAA was more frequent in V726A allele (16.9%) followed by M694V allele (12.3%). Elevated SAA levels were more frequent in patients on low colchicine doses. Forty-five percent (45%) of patients have low adherence to colchicine therapy. Interpretation and Conclusion. High SAA levels were detected two weeks after last FMF attack in a large percentage of Egyptian FMF children. This indicates that subclinical inflammation continues during attack-free periods, and SAA could be used as a marker of it. Hala M. Lofty, Huda Marzouk, Yomna Farag, Mohammad Nabih, Iman A. S. Khalifa, Noha Mostafa, Ahmed Salah, Laila Rashed, and Kamal El Garf Copyright © 2016 Hala M. Lofty et al. All rights reserved. Deferoxamine Suppresses Collagen Cleavage and Protease, Cytokine, and COL10A1 Expression and Upregulates AMPK and Krebs Cycle Genes in Human Osteoarthritic Cartilage Wed, 30 Nov 2016 06:11:35 +0000 http://www.hindawi.com/journals/ijr/2016/6432867/ This study reports the effects of the iron chelator deferoxamine (DFO) on collagen cleavage, inflammation, and chondrocyte hypertrophy in relation to energy metabolism-related gene expression in osteoarthritic (OA) articular cartilage. Full-depth explants of human OA knee articular cartilage from arthroplasty were cultured with exogenous DFO (1–50 μM). Type II collagen cleavage and phospho-adenosine monophosphate-activated protein kinase (pAMPK) concentrations were measured using ELISAs. Gene expression studies employed real-time PCR and included AMPK analyses in PBMCs. In OA explants collagen cleavage was frequently downregulated by 10–50 μM DFO. PCR analysis of 7 OA patient cartilages revealed that 10 μM DFO suppressed expression of MMP-1, MMP-13, IL-1β, and TNFα and a marker of chondrocyte hypertrophy, COL10A1. No changes were observed in the expression of glycolysis-related genes. In contrast, expressions of genes associated with the mitochondrial Krebs cycle (TCA), AMPK, HIF1α, and COL2A1 were upregulated. AMPK gene expression was reduced in OA cartilage and increased in PBMCs from the same patients compared to healthy controls. Our studies demonstrate that DFO is capable of suppressing excessive collagenase-mediated type II collagen cleavage in OA cartilage and reversing phenotypic changes. The concomitant upregulation of proanabolic TCA-related gene expressions points to a potential for availability of energy generating substrates required for matrix repair by end-stage OA chondrocytes. This might normally be prevented by high whole-body energy requirements indicated by elevated AMPK expression in PBMCs of OA patients. Elena V. Tchetina, Galina A. Markova, A. Robin Poole, David J. Zukor, John Antoniou, Sergey A. Makarov, and Aleksandr N. Kuzin Copyright © 2016 Elena V. Tchetina et al. All rights reserved. Association between Air Pollution and the Development of Rheumatic Disease: A Systematic Review Tue, 25 Oct 2016 12:31:23 +0000 http://www.hindawi.com/journals/ijr/2016/5356307/ Objective. Environmental risk factors, such as air pollution, have been studied in relation to the risk of development of rheumatic diseases. We performed a systematic literature review to summarize the existing knowledge. Methods. MEDLINE (1946 to September 2016) and EMBASE (1980 to 2016, week 37) databases were searched using MeSH terms and keywords to identify cohort, case-control, and case cross-over studies reporting risk estimates for the development of select rheumatic diseases in relation to exposure of measured air pollutants (). We extracted information on the population sample and study period, method of case and exposure determination, and the estimate of association. Results. There was no consistent evidence of an increased risk for the development of rheumatoid arthritis (RA) with exposure to NO2, SO2, PM2.5, or PM10. Case-control studies in systemic autoimmune rheumatic diseases (SARDs) indicated higher odds of diagnosis with increasing PM2.5 exposure, as well as an increased relative risk for juvenile idiopathic arthritis (JIA) in American children <5.5 years of age. There was no association with SARDs and NO2 exposure. Conclusion. There is evidence for a possible association between air pollutant exposures and the development of SARDs and JIA, but relationships with other rheumatic diseases are less clear. Gavin Sun, Glen Hazlewood, Sasha Bernatsky, Gilaad G. Kaplan, Bertus Eksteen, and Cheryl Barnabe Copyright © 2016 Gavin Sun et al. All rights reserved. Impact of Anti-Inflammatory Drugs on Pyogenic Vertebral Osteomyelitis: A Prospective Cohort Study Wed, 19 Oct 2016 14:06:06 +0000 http://www.hindawi.com/journals/ijr/2016/9345467/ Objective. Pyogenic vertebral osteomyelitis (PVO) are frequently misdiagnosed and patients often receive anti-inflammatory drugs for their back pain. We studied the impact of these medications. Methods. We performed a prospective study enrolling patients with PVO and categorized them depending on their drugs intake. Then, we compared diagnosis delay, clinical presentation at hospitalization, incidence of complications, and cure rate. Results. In total, 79 patients were included. Multivariate analysis found no correlation between anti-inflammatory drug intake and diagnosis delay, clinical presentation, complications, or outcome. Conclusion. Anti-inflammatory drugs intake does not affect diagnostic delay, severity at diagnosis, or complications of PVO. Aurélien Dinh, Maxime Jean, Frédérique Bouchand, Benjamin Davido, Alexis Descatha, Clara Duran, Guillaume Gras, Christian Perronne, Denis Mulleman, Jérôme Salomon, and Louis Bernard Copyright © 2016 Aurélien Dinh et al. All rights reserved. Risk of Malignant Neoplasm in Patients with Incident Rheumatoid Arthritis 1980–2007 in relation to a Comparator Cohort: A Population-Based Study Wed, 17 Aug 2016 14:25:20 +0000 http://www.hindawi.com/journals/ijr/2016/4609486/ Objective. To determine whether the incidence of malignancy is increased in patients with rheumatoid arthritis (RA) compared to a matched comparison cohort and to identify risk for any individual malignancy in RA. Methods. A cohort of 813 Olmsted County, Minnesota, residents who first fulfilled 1987 ACR criteria for RA in 1980–2007 was previously identified by medical record review. Medical records of 813 RA cases and a comparison cohort of age and sex matched Olmsted County residents without RA were evaluated retrospectively for cancer occurrence. Patients in both cohorts were followed until death, migration from Olmsted County, or 12/31/2014. Results. The RA and non-RA cohorts (mean age at incidence/index date: 55.9 [SD: 15.7] years; 68.4% females in both cohorts) were followed on average of 14.1 (SD: 7.7) and 14.9 (SD: 8.1) years, respectively. Prior to RA incidence/index date, 52 RA patients and 66 non-RA subjects had malignancies excluding NMSC (). During follow-up, significantly more malignancies occurred in patients with RA () than in comparator subjects (; hazard ratio: 1.32; ). Inclusion of NMSC obviated this difference. Conclusion. After excluding NMSC, there was a small to moderately increased risk of malignancies in patients with RA. Cancer surveillance is imperative in all patients with RA. Shafay Raheel, Cynthia S. Crowson, Kerry Wright, and Eric L. Matteson Copyright © 2016 Shafay Raheel et al. All rights reserved. Severity of Osteoarthritis Is Associated with Increased Arterial Stiffness Sun, 17 Jul 2016 07:55:36 +0000 http://www.hindawi.com/journals/ijr/2016/6402963/ Objective. Osteoarthritis (OA) is associated with increased cardiovascular comorbidity and mortality. Evidence is lacking about whether arterial stiffness is involved in OA. The objective of our study was to find out associations between OA, arterial stiffness, and adipokines. Design. Seventy end-stage knee and hip OA patients (age years) and 70 asymptomatic controls (age years) were investigated using the applanation tonometry to determine their parameters of arterial stiffness. Serum adiponectin, leptin, and matrix metalloproteinase 3 (MMP-3) levels were determined using the ELISA method. Correlation between variables was determined using Spearman’s rho. Multiple regression analysis with a stepwise selection procedure was employed. Results. Radiographic OA grade was positively associated with increased carotid-femoral pulse wave velocity (cf-PWV) (, ). We found that OA grade was also associated with leptin and MMP-3 levels (, and , , resp.). In addition, serum adiponectin level was positively associated with augmentation index and inversely with large artery elasticity index (, and , , resp.). Conclusions. Our results suggest that OA severity is independently associated with increased arterial stiffness and is correlated with expression of adipokines. Thus, increased arterial stiffness and adipokines might play an important role in elevated cardiovascular risk in end-stage OA. Kaspar Tootsi, Jaak Kals, Mihkel Zilmer, Kaido Paapstel, and Aare Märtson Copyright © 2016 Kaspar Tootsi et al. All rights reserved. Erratum to “The Characteristics and Significance of Locally Infiltrating B Cells in Lupus Nephritis and Their Association with Local BAFF Expression” Thu, 16 Jun 2016 07:05:11 +0000 http://www.hindawi.com/journals/ijr/2016/7513892/ Chuan-Yin Sun, Yan Shen, Xiao-Wei Chen, Yu-Cheng Yan, Feng-Xia Wu, Ming Dai, Ting Li, and Cheng-De Yang Copyright © 2016 Chuan-Yin Sun et al. All rights reserved. Cardiac Function and Diastolic Dysfunction in Behcet’s Disease: A Systematic Review and Meta-Analysis Tue, 10 May 2016 11:58:24 +0000 http://www.hindawi.com/journals/ijr/2016/9837184/ Background. Cardiovascular involvement in Behcet’s disease (BD) is reported and has variable manifestations. It is not clear if diastolic dysfunction (DD) is increased in BD. Our objective was to evaluate the existing literature to determine if cardiac dysfunction, particularly DD, was more prevalent in these patients. Methods. A systematic review and meta-analysis of the available studies analyzing the echocardiographic findings in BD was conducted using a random-effects model. Mean differences were used to calculate the effect sizes of the echocardiographic parameters of interest. Results. A total of 22 studies with 1624 subjects were included in the analysis. Patients with BD had statistically significantly larger mean left atrial dimension (0.08, ), greater aortic diameter (0.16, ), significantly reduced ejection fraction (−1.08, ), significantly prolonged mitral deceleration time (14.20, ), lower ratio (−0.24, ), and increased isovolumetric relaxation time (7.29, ). Conclusion. DD is increased in patients with BD by the presence of several echocardiographic parameters favoring DD as compared to controls. The meta-analysis also identified that LA dimension is increased in BD patients. EF has also been found to be lower in BD patients. Aortic diameter was also increased in BD patients as compared to controls. Fawad Aslam, Salman J. Bandeali, Cynthia Crowson, and Mahboob Alam Copyright © 2016 Fawad Aslam et al. All rights reserved. The Reliability of a Novel Automated System for ANA Immunofluorescence Analysis in Daily Clinical Practice Mon, 09 May 2016 07:12:11 +0000 http://www.hindawi.com/journals/ijr/2016/6019268/ Automated interpretation (AI) systems for antinuclear antibody (ANA) analysis have been introduced based on assessment of indirect immunofluorescence (IIF) patterns. The diagnostic performance of a novel automated IIF reading system was compared with visual interpretation (VI) of IIF in daily clinical practice to evaluate the reduction of workload. ANA-IIF tests of consecutive serum samples from patients with suspected connective tissue disease were carried out using HEp-2 cells according to routine clinical care. AI was performed using a visual analyser (Zenit G-Sight, Menarini, Germany). Agreement rates between ANA results by AI and VI were calculated. Of the 336 samples investigated, VI yielded 205 (61%) negative, 42 (13%) ambiguous, and 89 (26%) positive results, whereas 82 (24%) were determined to be negative, 176 (52%) ambiguous, and 78 (24%) positive by AI. AI displayed a diagnostic accuracy of 175/336 samples (52%) with a kappa coefficient of 0.34 compared to VI being the gold standard. Solely relying on AI, with VI only performed for all ambiguous samples by AI, would have missed 1 of 89 (1%) positive results by VI and misclassified 2 of 205 (1%) negative results by VI as positive. The use of AI in daily clinical practice resulted only in a moderate reduction of the VI workload (82 of 336 samples: 24%). Mohammed Alsuwaidi, Margit Dollinger, Martin Fleck, and Boris Ehrenstein Copyright © 2016 Mohammed Alsuwaidi et al. All rights reserved. SAPHIRE: Stress and Pulmonary Hypertension in Rheumatoid Evaluation—A Prevalence Study Wed, 20 Apr 2016 12:19:00 +0000 http://www.hindawi.com/journals/ijr/2016/4564531/ Pulmonary artery hypertension (PAH) is a disorder of elevated resistance in the pulmonary arterial vessels, reflected by elevation of measured pulmonary artery pressure (PAP), and presenting with breathlessness and, if untreated, progressing to right heart failure and death. The heightened prevalence of PAH in populations with underlying systemic autoimmune conditions, particularly scleroderma and its variants, is well recognised, consistent with the proposed autoimmune contribution to PAH pathogenesis, along with disordered thrombotic, inflammatory, and mitogenic factors. Rheumatoid arthritis (RA) is one of a group of systemic autoimmune conditions featuring inflammatory symmetrical erosive polyarthropathy as its hallmark. This study explored the prevalence of PAH in a population of unselected individuals with RA, using exercise echocardiography (EchoCG). The high prevalence of EchoCG-derived elevation of PAP (EDEPP) in this population (14%) suggests that, like other autoimmune conditions, RA may be a risk factor for PAH. Patients with RA may therefore represent another population for whom PAH screening with noninvasive tools such as EchoCG may be justified. G. E. M. Reeves, N. Collins, P. Hayes, J. Knapp, M. Squance, H. Tran, and B. Bastian Copyright © 2016 G. E. M. Reeves et al. All rights reserved. The Diagnostic Value of Alpha-1-Antitrypsin Phenotype in Patients with Granulomatosis with Polyangiitis Tue, 05 Apr 2016 14:15:31 +0000 http://www.hindawi.com/journals/ijr/2016/7831410/ The deficiency of alpha-1 protease inhibitor, or alpha-1-antitrypsin (A1AT), predisposes to chronic lung diseases and extrapulmonary pathology. Besides classical manifestations, such as pulmonary emphysema and liver disease, alpha-1-antitrypsin deficiency (A1ATD) is also known to be associated with granulomatosis with polyangiitis (GPA or Wegener’s granulomatosis). The aim of our study was to evaluate the frequency of allelic isoforms of A1AT and their clinical significance among GPA patients. Detailed clinical information, including Birmingham Vasculitis Activity Score (BVAS), incidence of lung involvement, anti-proteinase 3 (PR3) antibodies concentrations, and other laboratory data were collected in 38 GPA patients. We also studied serum samples obtained from 46 healthy donors. In all collected samples A1AT phenotyping by isoelectrofocusing (IEF) and turbidimetric A1AT measurement were performed. Abnormal A1AT variants were found in 18.4% (7/38) of cases: 1 ZZ, 4 MZ, 2 MF, and only 1 MZ in control group (2%). The mean A1AT concentration in samples with atypical A1AT phenotypes was significantly lower () than in normal A1AT phenotype. We found that patients with abnormal A1AT phenotypes had significantly higher vasculitis activity (BVAS) as well as anti-PR3 antibodies concentration. We conclude that A1AT deficiency should be considered in all patients with GPA. M. Y. Pervakova, V. L. Emanuel, O. N. Titova, S. V. Lapin, V. I. Mazurov, I. B. Belyaeva, A. L. Chudinov, T. V. Blinova, and E. A. Surkova Copyright © 2016 M. Y. Pervakova et al. All rights reserved. Vaccination of Adult Patients with Systemic Lupus Erythematosus in Portugal Wed, 16 Mar 2016 08:10:49 +0000 http://www.hindawi.com/journals/ijr/2016/2845617/ In the wake of the Portuguese vaccination program 50th anniversary it seems appropriate to review vaccination in patients with systemic lupus erythematosus. Controversial issues as regards the association between autoimmune diseases, infections, and vaccines are discussed as well as vaccine safety and efficacy issues as regards chronic immunosuppressant (IS) drug therapy. After a brief overview of national policies, specific recommendations are made as regards vaccination for adult patients with SLE with a particular focus on current IS therapy and unmet needs. Maria Francisca Moraes-Fontes, Ana Margarida Antunes, Heidi Gruner, and Nuno Riso Copyright © 2016 Maria Francisca Moraes-Fontes et al. All rights reserved. Joint Degradation in a Monkey Model of Collagen-Induced Arthritis: Role of Cathepsin K Based on Biochemical Markers and Histological Evaluation Tue, 02 Feb 2016 07:14:22 +0000 http://www.hindawi.com/journals/ijr/2016/8938916/ The role of cathepsin K in joint degradation in a model of collagen-induced arthritis (CIA) in cynomolgus monkey was examined using biochemical markers and histology. Joint swelling, urinary C-telopeptide of type II collagen (CTX-II), deoxypyridinoline (DPD), and N- and C-telopeptides of type I collagen (NTX and CTX-I, resp.) were analyzed. Immunohistochemistry of type II collagen, cathepsin K, and CTX-II were performed using joints. Joint swelling reached peak on day 42 and continued at this level. The CTX-II level peaked on day 28 and declined thereafter, while CTX-I, NTX, and DPD reached plateau on day 43. Joint swelling was positively correlated with CTX-II increases on days 20 and 42/43, with increases in CTX-I and NTX/Cr on days 42/43 and 84, and with DPD increases throughout the study period. Intense cathepsin K staining was observed in osteoclasts and in articular cartilage and synovial tissue in arthritic joints. CTX-II was present in the superficial layer of articular cartilage in CIA monkeys. Evidence from biochemical markers suggests that matrix degradation in the CIA model starts with degradation of cartilage, rather than bone resorption. Cathepsin K expressed in osteoclasts, articular cartilage, and synovial tissue may contribute to degradation of cartilage. Makoto Tanaka, Hiroyuki Yamada, Satoshi Nishikawa, Hiroshi Mori, Yasuo Ochi, Naoto Horai, Minqi Li, and Norio Amizuka Copyright © 2016 Makoto Tanaka et al. All rights reserved. Behcet’s Disease: Is There Geographical Variation? A Review Far from the Silk Road Sun, 20 Dec 2015 11:46:55 +0000 http://www.hindawi.com/journals/ijr/2015/945262/ Behcet’s Disease (BD) is a systemic vasculitis characterized by the triad of recurrent mouth and genital ulcers with eye involvement. To date there are no laboratory tests specific for the disease and diagnosis continues to remain on clinical grounds. Multiple criteria have been created as guides for diagnosis; however, given the wide spectrum of organ involvement, some cases remain undiagnosed. The diagnosis of Behcet’s Disease may only be made over time as the clinical manifestations emerge sometimes separated by months and even years. With an increased recognition of this disease it has become apparent that there is geographical variation in clinical manifestations. In particular cardiac manifestations are not seen commonly in Caucasians compared to Asian and Middle Eastern patients, while neurological manifestations are more common in Caucasians. Use of immunosuppressive and immunomodulatory drugs to suppress inflammation remains the cornerstone of treatment. Nieves Marie Leonardo and Julian McNeil Copyright © 2015 Nieves Marie Leonardo and Julian McNeil. All rights reserved. Clinical Assessment and Management of Spondyloarthritides in the Middle East: A Multinational Investigation Thu, 17 Dec 2015 11:15:58 +0000 http://www.hindawi.com/journals/ijr/2015/178750/ Data on spondyloarthritis (SpA) from the Middle East are sparse and the management of these diseases in this area of the world faces a number of challenges, including the relevant resources to enable early diagnosis and referral and sufficient funds to aid the most appropriate treatment strategy. The objective was to report on the characteristics, disease burden, and treatment of SpA in the Middle East region and to highlight where management strategies could be improved, with the overall aim of achieving better patient outcomes. This multicenter, observational, cross-sectional study collected demographic, clinical, laboratory, and treatment data on 169 consecutive SpA patients at four centers (Egypt, Kuwait, Qatar, and Saudi Arabia). The data collected presents the average time from symptom onset to diagnosis along with the presence of comorbidities in the region and comparisons between treatment with NSAIDs and biologics. In the absence of regional registries of SpA patients, the data presented here provide a rare snapshot of the characteristics, disease burden, and treatment of these patients, highlighting the management challenges in the region. Mohammed Hammoudeh, Hanan Al Rayes, Adel Alawadhi, Kamel Gado, Khalid Shirazy, and Atul Deodhar Copyright © 2015 Mohammed Hammoudeh et al. All rights reserved. Serum Markers in Rheumatoid Arthritis: A Longitudinal Study of Patients Undergoing Infliximab Treatment Wed, 16 Dec 2015 13:54:21 +0000 http://www.hindawi.com/journals/ijr/2015/276815/ Objective. The aim of this study was to investigate the clinical effect and serum markers in a cohort of rheumatoid arthritis patients with moderate to high disease activity, participating in an open clinical phase IV study conducted in Norway between 2001 and 2003 receiving infliximab treatment. Method. A total of 39 patients were studied, with a mean age of 54 years and 12-year disease duration. The analyses were performed using serum from patients at four assessment time points: baseline and 3, 6, and 12 months after starting treatment with infliximab. A wide variety of clinical data was collected and disease activity of 28 joints and Simple Disease Activity Index were calculated. The joint erosion was determined by X-ray imaging and the Sharp/van der Heijde score was determined. Serum analysis included multiplex immunoassays for 12 cytokines, 5 matrix metalloproteases, and 2 VEGFs. Results. The majority of the RA patients in this study had initially moderate to high disease activity and the infliximab treatment reduced the disease activity significantly and also reduced any further joint destruction and improved disease status. Most of the serum levels of cytokines and metalloproteases remained unchanged during the course of the study, and we were unable to detect changes in TNF-α in serum. Serum levels of IL-6 and VEGF-A decreased significantly after initiation of infliximab treatment. Conclusion. The serum levels of IL-6 and VEGF-A may be promising disease markers as they vary with disease progression. The clinical significance of these findings is yet to be determined and has to be confirmed in future clinical trials before being applied in the clinics. Oddgeir Selaas, Hilde H. Nordal, Anne-Kristine Halse, Johan G. Brun, Roland Jonsson, and Karl A. Brokstad Copyright © 2015 Oddgeir Selaas et al. All rights reserved. Improving the Measurement of Disease Activity for Patients with Rheumatoid Arthritis: Validation of an Electronic Version of the Routine Assessment of Patient Index Data 3 Sun, 08 Nov 2015 13:12:33 +0000 http://www.hindawi.com/journals/ijr/2015/834070/ Introduction. An electronic Routine Assessment of Patient Index Data 3 (RAPID 3) was incorporated into our electronic health records (EHRs) which did not replicate the visual presentation of the paper version. This study validated the electronic RAPID 3 compared to the paper version. Methods. Rheumatoid arthritis (RA) patients () completed both the electronic RAPID 3 online in the week prior to and a paper version on the day of their clinic visit. Results. Paired t-test showed no significant difference ( value = 0.46) between versions. Conclusion. The electronic version of RAPID 3 is valid and can be easily integrated in care of RA patients. Ruthie M. Chua, John N. Mecchella, and Alicia J. Zbehlik Copyright © 2015 Ruthie M. Chua et al. All rights reserved. Gastric Antral Vascular Ectasia in Systemic Sclerosis: Current Concepts Sun, 08 Nov 2015 13:04:32 +0000 http://www.hindawi.com/journals/ijr/2015/762546/ Introduction. Gastric antral vascular ectasia (GAVE) is a rare entity with unique endoscopic appearance described as “watermelon stomach.” It has been associated with systemic sclerosis but the pathophysiological changes leading to GAVE have not been explained and still remain uncertain. Methods. Databases Medline, Scopus, Embase, PubMed, and Cochrane were searched for relevant papers. The main search words were “Gastric antral vascular ectasia,” “Watermelon Stomach,” “GAVE,” “Scleroderma,” and “Systemic Sclerosis.” Fifty-four papers were considered for this review. Results. GAVE is a rare entity in the spectrum of manifestations of systemic sclerosis with unknown pathogenesis. Most patients with systemic sclerosis and GAVE present with asymptomatic anemia, iron deficiency anemia, or heavy acute gastrointestinal bleeding. Symptomatic therapy and endoscopic ablation are the first-line of treatment. Surgical approach may be recommended for patients who do not respond to medical or endoscopic therapies. Conclusion. GAVE can be properly diagnosed and treated. Early diagnosis is key in the management of GAVE because it makes symptomatic therapies and endoscopic approaches feasible. A high index of suspicion is critical. Future studies and a critical review of the current findings about GAVE are needed to understand the role of this condition in systemic sclerosis. Raphael Hernando Parrado, Hernan Nicolas Lemus, Paola Ximena Coral-Alvarado, and Gerardo Quintana López Copyright © 2015 Raphael Hernando Parrado et al. All rights reserved. Gynaecological Screening for Cervical and Vulvar Malignancies in a Cohort of Systemic Sclerosis Patients: Our Experience and Review of the Literature Sun, 18 Oct 2015 14:39:55 +0000 http://www.hindawi.com/journals/ijr/2015/761867/ Background. Increased incidence of cancer was frequently reported in scleroderma (SSc), but no association with gynaecological malignancies was described in literature. Objectives. To investigate gynaecological neoplasms in SSc patients. Methods. In this cross-sectional analysis, we evaluated 80 SSc patients, living in the same geographical area. We considered all patients undergoing gynaecological evaluation, including pap test as screening for cervical cancer, between January 2008 and December 2014. Results. 55 (68.7%) patients were negative and 20 (25%) presented inflammatory alterations, while cancer or precancerous lesions were found in 5 (6.2%) cases (2 showed cervical cancer (one of them in situ), 1 vulvar melanoma, 1 vulvar intraepithelial neoplasia, and 1 endocervical polyp with immature squamous metaplasia). The frequency of cervical cancer in our series seems higher in comparison to the incidence registered in the same geographical area. The presence of atypical cytological findings correlated with anti-Scl70 autoantibodies (p = 0.022); moreover, the patients with these alterations tended to be older (median 65, range 46–67), if compared to the whole series (p = 0.052). Conclusions. A relatively high frequency of gynaecological malignancies was found in our SSc series. In general, gynaecological evaluation for SSc women needs to be included in the routine patients’ surveillance. M. Colaci, D. Giuggioli, G. Cassone, C. Vacchi, F. Campomori, F. Boselli, M. Sebastiani, A. Manfredi, and C. Ferri Copyright © 2015 M. Colaci et al. All rights reserved. Level of Adherence to Prophylactic Osteoporosis Medication amongst Patients with Polymyalgia Rheumatica and Giant Cell Arteritis: A Cross-Sectional Study Tue, 29 Sep 2015 08:54:29 +0000 http://www.hindawi.com/journals/ijr/2015/783709/ Objective. To estimate level of adherence to oral calcium and vitamin D supplementation as well as bisphosphonate amongst patients with PMR and GCA treated with glucocorticoids. Method. A total of 138 patients with the diagnosis of PMR and/or GCA registered in our department in December 2013. In this cross-sectional study we interviewed all the patients to measure level of adherence to calcium and vitamin D, as well as bisphosphonates. Results. Out of the 118 included patients, 88.9% of them were adherent to their prescription. Only 2 patients (1.7%) did not take calcium and vitamin D at all and 10 patients (8.5%) took their medication infrequently, 9 and 1 out of 10 patients took the medication 50–100% of the time and less than 50% of the prescribed dose, respectively. Sixty-one patients received additional treatment with bisphosphonate and 96.6% were adherent to this therapy. The remaining 3.4% of the patients did not take the medication at all. Forgetfulness, adverse side effects, and lack of understanding of treatment benefits were the most significant causes for nonadherence to calcium and vitamin D. Conclusions. Contrary to what we expected this study found that adherence to osteoporosis preventive medication in patients with PMR and GCA was high. A. Emamifar, Rannveig Gildberg-Mortensen, S. Andreas Just, N. Lomborg, R. Asmussen Andreasen, and I. M. Jensen Hansen Copyright © 2015 A. Emamifar et al. All rights reserved.