International Journal of Rheumatology The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Severity of Osteoarthritis Is Associated with Increased Arterial Stiffness Sun, 17 Jul 2016 07:55:36 +0000 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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. Rheumatic Heart Disease in Kerala: A Vanishing Entity? An Echo Doppler Study in 5–15-Years-Old School Children Mon, 14 Sep 2015 06:23:00 +0000 Background. Early detection of subclinical rheumatic heart disease by use of echocardiography warrants timely implementation of secondary antibiotic prophylaxis and thereby prevents or retards its related complications. Objectives. The objective of this epidemiological study was to determine prevalence of RHD by echocardiography using World Heart Federation criteria in randomly selected school children of Trivandrum. Methods. This was a population-based cross-sectional screening study carried out in Trivandrum. A total of 2060 school children, 5–15 years, were randomly selected from five government and two private (aided) schools. All enrolled children were screened for RHD according to standard clinical and WHF criteria of echocardiography. Results. Echocardiographic examinations confirmed RHD in 5 children out of 146 clinically suspected cases. Thus, clinical prevalence was found to be 2.4 per 1000. According to WHF criteria of echocardiography, 12 children (12/2060) were diagnosed with RHD corresponding to echocardiographic prevalence of 5.83 cases per 1000. As per criteria, 6 children were diagnosed with definite RHD and 6 with borderline RHD. Conclusions. The results of the current study demonstrate that echocardiography is more sensitive and feasible in detecting clinically silent RHD. Our study, the largest school survey of south India till date, points towards declining prevalence of RHD (5.83/1000 cases) using WHF criteria in Kerala. Bigesh Nair, Sunitha Viswanathan, A. George Koshy, Prabha Nini Gupta, Namita Nair, and Ashok Thakkar Copyright © 2015 Bigesh Nair et al. All rights reserved. Familial Mediterranean Fever in Iran: A Report from FMF Registration Center Thu, 27 Aug 2015 13:31:58 +0000 Background. Familial Mediterranean fever (FMF) is a periodic AR autoinflammatory disorder. This comprehensive study describes FMF in Iran as a country near Mediterranean area. Materials and Methods. From the country FMF registration center 403 patients according to Tel-Hashomer criteria enrolled this study, 239 patients had MEFV gene mutations analyses. Data, if needed, was analyzed by SPSS v20. Results. 175 patients (43.4%) were female and 228 patients (56.6%) were male. The mean age was 21.3 years. Abdominal pain was in 93.3% patients and 88.1% had fever. Abdominal pain was the main complaint of patients in (49.6%). The mean interval between attacks was days and the mean duration of every episodes was hours. 15.1% of patients had positive family history and 12.7% had previous surgery; in 52.3% of patients delay in diagnosis was more than three years. 12 common MEFV gene mutations were analyzed, 21.33% were without mutations, 39.7% had compound heterozygote, 25.52% showed heterozygous, and 13.38% showed homozygous results. The most common compound genotype was M694V-V726A (% 10.46) and in alleles M694V (% 20.9) and V726A (% 12.7) were the most frequent mutations, respectively. Conclusion. M694V was the most common mutation, and the most common compound genotype was M694V-V726A. Our genotype results are similar to Arabs and in some way to Armenians, erysipelas-like skin lesions are not common in this area, and clinical criteria are the preferred methods in diagnosis of FMF. Farhad Salehzadeh Copyright © 2015 Farhad Salehzadeh. All rights reserved. Comment on “The Role of Citrullinated Protein Antibodies in Predicting Erosive Disease in Rheumatoid Arthritis: A Systematic Literature Review and Meta-Analysis” Sun, 23 Aug 2015 12:38:18 +0000 Shailendra Kapoor Copyright © 2015 Shailendra Kapoor. All rights reserved. Rheumatoid Arthritis and the Cervical Spine: A Review on the Role of Surgery Mon, 17 Aug 2015 11:14:30 +0000 Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease affecting a significant percentage of the population. The cervical spine is often affected in this disease and can present in the form of atlantoaxial instability (AAI), cranial settling (CS), or subaxial subluxation (SAS). Patients may present with symptoms and disability secondary to these entities but may also be neurologically intact. Cervical spine involvement in RA can pose a challenge to the clinician and the appropriate role of surgical intervention is controversial. The aim of this paper is to describe the pathology, pathophysiology, clinical manifestations, and diagnostic evaluation of rheumatoid arthritis in the cervical spine in order to provide a better understanding of the indications and options for surgery. Both the medical and surgical treatment options for RA have improved, so has the prognosis of the cervical spine disease. With the advent of disease modifying antirheumatic drugs (DMARDs), fewer patients are presenting with cervical spine manifestations of RA; however, those that do, now have improved surgical techniques available to them. We hope that, by reading this paper, the clinician is able to better evaluate patients with RA in the cervical spine and determine in which patients surgery is indicated. John L. Gillick, John Wainwright, and Kaushik Das Copyright © 2015 John L. Gillick et al. All rights reserved. Total Hip Arthroplasty in Systemic Lupus Erythematosus: A Systematic Review Wed, 08 Jul 2015 12:43:38 +0000 The prognosis of systemic lupus erythematosus (SLE) has greatly improved in recent years, resulting in an increased number of patients reporting musculoskeletal complications such as osteonecrosis of the femoral head. Total hip arthroplasty (THA) can be utilised to alleviate the pain associated with this; however postoperative outcomes in patients with SLE are uncertain. A systematic review of the literature was conducted to identify articles presenting results of THA in SLE, and nine suitable papers were found. All papers were level IV evidence. Pooling the results, a total of 162 patients underwent 214 total hip arthroplasties. Mean follow-up was 72.5 months. The mean Harris Hip Score improved from 45.5 preoperatively to 88.6 and last follow-up. Seventeen percent of patients experienced at least one complication. Superficial wound infection occurred in 3.3%. Revision was required in 2.8% of cases. The mortality rate was 18.5% however no deaths were attributable to undergoing THA. Given the paucity of data present in the literature, more studies are required to adequately assess the postoperative outcomes of THA in patients with SLE, particularly complication rates. John W. Kennedy and Wasim Khan Copyright © 2015 John W. Kennedy and Wasim Khan. All rights reserved. Current Concepts in the Management of Rheumatoid Hand Wed, 08 Jul 2015 12:24:35 +0000 Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by a T cell-driven autoimmune process, which majorly involves the diarthrodial joints. It affects 1% of the US population, and approximately 70% of patients with RA develop pathologies of the hand, especially of the metacarpophalangeal joints (MCP). Furthermore, also the extensor and flexor tendons of the fingers are frequently involved. The first line of treatment should be conservative. Three general classes of drugs are currently available for RA: nonsteroidal anti-inflammatory agents (NSAIDs), corticosteroids, and disease modifying antirheumatic drugs (DMARDs). Encouraging results have been obtained using DMARDs. However, when severe deformities occur or when patients are unresponsive to medical management and injections therapy, surgical intervention should be performed to relieve pain and restore function. Several surgical options have been described for the management of MCP joint deformities, including soft tissue procedures, arthrodesis, and prosthetic replacement. Tendons ruptures are generally managed with tendon transfer surgery, while different surgical procedures are available to treat fingers deformities. The aim of the present review is to report the current knowledge in the management of MCP joint deformities, as well as tendons damage and fingers deformities, in patients with RA. Umile Giuseppe Longo, Stefano Petrillo, and Vincenzo Denaro Copyright © 2015 Umile Giuseppe Longo et al. All rights reserved. An Insight into Methods and Practices in Hip Arthroplasty in Patients with Rheumatoid Arthritis Wed, 08 Jul 2015 11:14:05 +0000 Total hip arthroplasty (THA) has improved the quality of life of patients with hip arthritis. Orthopedic community is striving for excellence to improve surgical techniques and postoperative care. Despite these efforts, patients continue facing postoperative complications. In particular, patients with rheumatoid arthritis display a higher risk of certain complications such as dislocation, periprosthetic infection, and shorter prosthesis durability. In this review we present the current knowledge of hip arthroplasty in patients with rheumatoid arthritis with more insight into common practices and interventions directed at enhancing recovery of these patients and current shortfalls. Mohammad Saeed Mosleh-shirazi, Mazin Ibrahim, Philip Pastides, Wasim Khan, and Habib Rahman Copyright © 2015 Mohammad Saeed Mosleh-shirazi et al. All rights reserved. Safety, Tolerability, and Efficacy of Tocilizumab in Rheumatoid Arthritis: An Open-Label Phase 4 Study in Patients from the Middle East Tue, 19 May 2015 14:41:44 +0000 This open-label study investigated the safety and efficacy of tocilizumab in Middle Eastern patients with rheumatoid arthritis (RA). Patients whose Disease Activity Score based on 28 joints (DAS28) was >3.2 received tocilizumab 8 mg/kg intravenously every 4 weeks for 24 weeks. Patients receiving aTNF ± nonbiologic disease-modifying antirheumatic drug(s) (DMARD(s)) switched to tocilizumab; patients receiving nonbiologic DMARD monotherapy added tocilizumab. Primary end points were adverse events (AEs), serious AEs (SAEs), and laboratory parameters; secondary end points were DAS28, Health Assessment Questionnaire-Disability Index, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Eighty-eight of 95 patients completed 24 weeks. Overall, 125 AEs were reported in 43 (45%) patients; the most common were increased hepatic enzymes (16%) and cholesterol (11%). Eight patients experienced SAEs. Significant changes from baseline to week 24 occurred for hemoglobin, neutrophils, platelets, total cholesterol, and liver enzymes (). DAS28, CRP, and ESR decreased significantly from baseline at each visit (). At week 24, the proportions of patients reporting DAS28 clinically meaningful improvement (decrease ≥1.2), low disease activity (DAS28 ≥2.6 to ≤3.2), and remission (DAS28 <2.6) were 92%, 23%, and 64%, respectively. Safety and efficacy of tocilizumab were consistent with values reported in Western patients. Mohammed Hammoudeh, Adel Al Awadhi, Eman Haji Hasan, Maassoumeh Akhlaghi, Arman Ahmadzadeh, and Bahar Sadeghi Abdollahi Copyright © 2015 Mohammed Hammoudeh et al. All rights reserved. Evaluation of Ovarian Reserve with Anti-Müllerian Hormone in Familial Mediterranean Fever Tue, 12 May 2015 07:16:49 +0000 Objective. To investigate ovarian reserves in attack-free familial Mediterranean fever (AF-FMF) patients at the reproductive age by anti-Müllerian hormone (AMH), antral follicle count (AFC), ovarian volume, and hormonal parameters. Methods. Thirty-three AF-FMF patients aging 18–45 years and 34 healthy women were enrolled and FSH, LH, E2, PRL, and AMH levels were measured in the morning blood samples at 2nd–4th days of menstruation by ELISA. Concomitant pelvic ultrasonography was performed to calculate AFC and ovarian volumes. Results. In FMF patient group, median AMH levels were statistically significantly lower in the M69V mutation positive group than in the negative ones (). There was no statistically significant difference in median AMH levels between E148Q mutation positive patients and the negative ones (). There was also no statistically significant difference in median AMH levels between M680I mutation positive patients and the negative ones (). No statistically significant difference was observed in median AMH levels between patients who had at least one mutation and those with no mutations (). We realized that there was no difference in comparisons between ovarian volumes, number of follicles, and AMH levels ovarian reserves when compared with FMF patients and healthy individuals. Conclusions. Ovarian reserves of FMF pateints were similar to those of healthy subjects according to AMH. However, AMH levels were lower in FMF patients with M694V mutation. Ali Şahin, Savaş Karakuş, Yunus Durmaz, Çağlar Yıldız, Hüseyin Aydın, Ahmet Kıvanç Cengiz, and Duygu Güler Copyright © 2015 Ali Şahin et al. All rights reserved. Intravenous Iron Administration and Hypophosphatemia in Clinical Practice Mon, 27 Apr 2015 08:12:00 +0000 Introduction. Parenteral iron formulations are frequently used to correct iron deficiency anemia (IDA) and iron deficiency (ID). Intravenous formulation efficacy on ferritin and hemoglobin level improvement is greater than that of oral formulations while they are associated with lower gastrointestinal side effects. Ferric carboxymaltose- (FCM-) related hypophosphatemia is frequent and appears without clinical significance. The aim of this study was to assess the prevalence, duration, and potential consequences of hypophosphatemia after iron injection. Patients and Methods. The medical records of all patients who underwent parenteral iron injection between 2012 and 2014 were retrospectively reviewed. Pre- and postinjection hemoglobin, ferritin, plasma phosphate, creatinine, and vitamin D levels were assessed. Patients who developed moderate (range: 0.32–0.80 mmol/L) or severe (<0.32 mmol/L) hypophosphatemia were questioned for symptoms. Results. During the study period, 234 patients received iron preparations but 104 were excluded because of missing data. Among the 130 patients included, 52 received iron sucrose (FS) and 78 FCM formulations. Among FS-treated patients, 22% developed hypophosphatemia versus 51% of FCM-treated patients, including 13% who developed profound hypophosphatemia. Hypophosphatemia severity correlated with the dose of FCM () but not with the initial ferritin, hemoglobin, or vitamin D level. Mean hypophosphatemia duration was 6 months. No immediate clinical consequence was found except for persistent fatigue despite anemia correction in some patients. Conclusions. Hypophosphatemia is frequent after parenteral FCM injection and may have clinical consequences, including persistent fatigue. Further studies of chronic hypophosphatemia long-term consequences, especially bone assessments, are needed. S. Hardy and X. Vandemergel Copyright © 2015 S. Hardy and X. Vandemergel. All rights reserved. Ectopic Germinal Centers and IgG4-Producing Plasmacytes Observed in Synovia of HLA-B27+ Ankylosing Spondylitis Patients with Advanced Hip Involvement Sun, 12 Apr 2015 08:59:06 +0000 Introduction. Ectopic lymphoid neogenesis and the presence of IgG4-positive plasmacytes have been confirmed in chronic inflammatory sclerosing diseases. This study aims to investigate hip synovial tissues of ankylosing spondylitis (AS) patients for IgG4-positive plasma cells and ectopic lymphoid tissues with germinal centers (GCs). Methods. Synovial samples were collected from 7 AS patients who received total hip replacement and were evaluated using immunohistochemistry for the presence of CD20+ B-cells, CD3+ T-cells, CD21+ follicular dendritic cells (FDC), and CD38+ plasma cells. Furthermore, immunoglobulin G (IgG and IgG4), IgA, IgM, and complement components C3d and C4d in synovia were evaluated. Both synovial CD21+ FDCs and IgG4-producing plasmacytes were analyzed. Results. All seven patients had severe fibrosis. Massive infiltrations of lymphocytes were found in 5 out of 7 patients’ synovia. Ectopic lymphoid tissues with CD21+ FDC networks and IgG4-positive plasma cells were observed coincidentally in two patients’ synovia. Conclusion. The pathophysiological mechanism of AS patients’ hip damage might be related to the coincidental presence of ectopic lymphoid tissue with FDCs network and IgG4-positive plasma cells identified here for the first time in AS patients’ inflamed synovial tissue. Xiugao Feng, Xiangjin Xu, Yue Wang, Zhiyong Zheng, and Guiying Lin Copyright © 2015 Xiugao Feng et al. All rights reserved. Development and Implementation of a Double-Blind Corticosteroid-Tapering Regimen for a Clinical Trial Tue, 24 Mar 2015 12:27:54 +0000 We describe the design and operationalization of a blinded corticosteroid-tapering regimen for a randomized trial of tocilizumab in giant cell arteritis (GCA). To our knowledge, no clinical trial in any disease has ever employed a blinded corticosteroid-tapering regimen, but this was necessary to the design of our trial which is likely to be relevant to other investigations of steroid-sparing regimens. Two standardized corticosteroid-tapering regimens are required for this GCA trial: a 6-month regimen in 3 arms (taken with tocilizumab 162 mg subcutaneously weekly or every other week or with placebo) and a 12-month regimen with placebo (fourth arm). Investigators select initial prednisone doses, tapered in an open-label fashion until 20 mg/day. Doses <20 mg/day are blinded. At least 27 blinded blister packs are required to ensure blinding and encourage compliance. This permits all possible daily doses but requires ≤5 capsules/day. The number of capsules taken at any point during tapering is identical across groups. Our approach may be extrapolated to trials beyond GCA. Neil Collinson, Katie Tuckwell, Frank Habeck, Monique Chapman, Micki Klearman, and John H. Stone Copyright © 2015 Neil Collinson et al. All rights reserved. The Role of Citrullinated Protein Antibodies in Predicting Erosive Disease in Rheumatoid Arthritis: A Systematic Literature Review and Meta-Analysis Wed, 04 Mar 2015 13:27:39 +0000 Background. Autoantibodies to citrullinated peptides have been shown to be valuable in the diagnosis of rheumatoid arthritis (RA). The expanding repertoire of antibodies to citrullinated peptide antigens (ACPA) has been a topic of great interest in recent reviews and research studies, as has the ability of these autoantibodies to predict disease outcome. Objectives. The aim of this review was to provide an update on the relevance of ACPA as prognostic markers in RA. The ability to identify patients predisposed to an aggressive outcome at the time of initial diagnosis greatly facilitates the selection of appropriate and cost-effective treatment. Methods. A systematic review of the literature was carried out. Studies from 1967 up to June 2014 with data on prognostic value of ACPA were included. Quality assessment was done by using the modified Hayden list for prognostic studies. Meta-analysis was performed using BioStat software. Results. The results of 25 studies were selected for the final review. A total of 6421 patients with RA were included, mainly in inception cohorts, with follow-up duration ranging from one year to ten years. All studies carried prognostic data on all available isotypes of anticyclic citrullinated protein (CCP), while four had data on antimutated citrullinated vimentin (MCV). There was a single relevant study each on anticitrullinated enolase peptide 1 (CEP1) and antichimaeric fibrin/filaggrin citrullinated peptide 1 (CFFCP1). All studies showed ACPA to be strong predictors of joint erosions in RA. Other factors, particularly baseline erosions, showed an additive effect. Anti-MCV appeared to be a marker of a more aggressive form of disease. Ten studies had data on which a meta-analysis could be performed. This gave an overall odds ratio of 4.85 for ACPA (anti-CCP/MCV) positivity being predictive for the development of joint erosions. Two studies with data on anti-CEP1 and anti-CFFCP1 also showed this positive predictive role of ACPA for joint erosions. Conclusions. ACPA are strong predictors of severity in RA. Their use should be part of routine rheumatology practice. A. A. Jilani and C. G. Mackworth-Young Copyright © 2015 A. A. Jilani and C. G. Mackworth-Young. All rights reserved. Asymptomatic Atherosclerosis in Egyptian Rheumatoid Arthritis Patients and Its Relation to Disease Activity Sun, 08 Feb 2015 07:11:26 +0000 Aim. To detect the frequency of subclinical atherosclerosis in rheumatoid arthritis patients without clinically evident atherosclerosis and to correlate its presence with the disease activity. Patients and Methods. Our study includes 112 RA patients (group 1) and 40 healthy controls (group 11). All patients and controls were subjected to full history taking, clinical examination, and laboratory investigations. Carotid intima media wall thickness (IMT) and carotid plaques were measured in both groups by B-mode ultrasonography; also color duplex Doppler ultrasound of the brachial artery was done to detect endothelial function. Results. There is atherosclerosis in 31.3% of asymptomatic RA patients compared with only 5% in controls . A significant difference was detected in patients with and without atherosclerosis regarding duration of the disease and patient’s age . There is highly statistical significant correlation between atherosclerosis and disease activity index. Conclusion. The frequency of subclinical atherosclerosis was high in long-term active RA patients. Rawhya R. Elshereef, Aymen Darwish, Amal Ali, Mohammed Abdel-kadar, and Lamiaa Hamdy Copyright © 2015 Rawhya R. Elshereef et al. All rights reserved. Prevalence of Hyposalivation in Patients with Systemic Lupus Erythematosus in a Brazilian Subpopulation Sun, 11 Jan 2015 13:25:53 +0000 Background. Systemic lupus erythematosus (SLE) is a chronic inflammatory, multisystem, and autoimmune disease. Objective. The aim of this study was to describe the prevalence of hyposalivation in SLE patients and evaluate factors associated. Methods. This is a cross-sectional study developed at the Cuiaba University General Hospital (UNIC-HGU), Mato Grosso, Brazil. The study population consisted of female SLE patients treated at this hospital from 06/2010 to 12/2012. Unstimulated salivary flow rates (SFRs) were measured. Descriptive and inferential analyses were performed in all cases using a significance level . Results. The results showed that 79% of patients with systemic lupus erythematosus suffered from hyposalivation and that the disease activity and age in years were the factors that resulted in statistically significant differences. Conclusion. The activity of the disease, age >27 years, and the drugs used were factors associated with hyposalivation, resulting in a statistically significant decrease in saliva production. Cristhiane Almeida Leite, Marcial Francis Galera, Mariano Martínez Espinosa, Paulo Ricardo Teles de Lima, Vander Fernandes, Álvaro Henrique Borges, and Eliane Pedra Dias Copyright © 2015 Cristhiane Almeida Leite et al. All rights reserved.