International Journal of Rheumatology The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . 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. Process Evaluation of Workplace Interventions with Physical Exercise to Reduce Musculoskeletal Disorders Wed, 10 Dec 2014 07:11:06 +0000 Process evaluation is important to explain success or failure of workplace interventions. This study performs a summative process evaluation of workplace interventions with physical exercise. As part of a randomized controlled trial 132 office workers with neck and shoulder pain were to participate in 10 weeks of elastic resistance training five times a week at the workplace; the 2 min group performed a single set of lateral raise to failure, and the 12 min group performed 5-6 sets with 8–12 repetitions. Participants received a single instructional session together with a training diary and manual at baseline (100% dose delivered and 100% dose received), and 59 and 57 participants, respectively, replied to the process evaluation questionnaire at 10-week follow-up. Results showed that in the 2 and 12 min groups, respectively, 82% and 81% of the participants completed more than 30 training sessions. However, two-thirds of the participants would have preferred more than a single exercise to vary between. In the 12 versus 2 min group more participants experienced the training sessions as too long (30% versus 5%). Most participants (67–92%) found the training diary and manual helpful, adequacy in a single instructional session, and satisfaction with the type of training. Among those with low adherence, lack of time (51%) and difficulties in starting exercising after illness (26%) were common barriers for regular training. Among those with low adherence, 52% felt that five training sessions per week were too much, and 29% would rather have trained a completely different kind of exercise. In conclusion, resistance training at the workplace is generally well received among office workers with neck-shoulder pain, but a one-size-fits-all approach is not feasible for all employees. Lars L. Andersen and Mette K. Zebis Copyright © 2014 Lars L. Andersen and Mette K. Zebis. All rights reserved. Pain Mystery Score Beliefs: A Comparison of Fibromyalgia and Rheumatoid Arthritis Tue, 09 Dec 2014 00:10:11 +0000 Objectives. To compare the mysteriousness scores of the Pain Beliefs and Perceptions Inventory in fibromyalgia. Methods. Two cohorts of patients, one with fibromyalgia (FM) and one with rheumatoid arthritis (RA), completed the Mystery Scale component of the Pain Beliefs and Perceptions Inventory to determine whether subjects in the two diagnostic groups had significantly different scores on the Mystery Scale. Results. A total of 126 subjects (64 FM, 62 RA) completed all questionnaires. The FM group had a greater percentage of female subjects, more severe pain, more severe anxiety, more severe depression, and a higher perceived injustice score. When the RA and FM group scores for the Mystery Scale were adjusted for age, sex, pain severity, HADS scores, and perceived injustice scores, the FM group still had a higher Mystery Scale score. Discussion. Fibromyalgia is associated with a higher level of perception of mysteriousness in the Pain Beliefs and Perceptions Inventory than is seen with rheumatoid arthritis. This difference appears to be independent of levels of pain, depression, anxiety, and perceived injustice. This sense of mysteriousness may reflect a lack of understanding of pain in fibromyalgia as previously reported and may be an area to be addressed in therapy. Robert Ferrari and Anthony Science Russell Copyright © 2014 Robert Ferrari and Anthony Science Russell. All rights reserved. Vitamin D Levels Are Associated with Expression of SLE, but Not Flare Frequency Mon, 24 Nov 2014 08:05:30 +0000 This study explores links between vitamin D deficiency (25(OH)D = 50 nmol/L) and serological autoimmunity (ANA > 1 : 80) and frequency of self-reported flares (SRF) in participants with clinical autoimmunity (SLE). 25(OH)D levels of 121 females were quantified and compared. The cohort consisted of 80 ACR defined SLE patients and 41 age and sex matched controls. Association analysis of log2 (25(OH)D) levels and ANA 80 positivity was undertaken via two-sample -tests and regression models. Significant differences were found for 25(OH)D levels (mean: control 74 nmol/L (29.5 ng/ml); SLE 58 nmol/L (23.1 ng/ml), ), 25(OH)D deficiency (). Regression models indicate that, for a twofold rise in 25(OH)D level, the odds ratio (OR) for ANA-positivity drops to 36% of the baseline OR. No link was found between SRF-days and 25(OH)D levels. Our results support links between vitamin D deficiency and expression of serological autoimmunity and clinical autoimmunity (SLE). However, no demonstrable association between 25(OH)D and SRF was confirmed, suggesting independent influences of other flare-inducing factors. Results indicate that SLE patients have high risk of 25(OH)D deficiency and therefore supplementation with regular monitoring should be considered as part of patient management. Marline L. Squance, Glenn E. M. Reeves, and Huy A. Tran Copyright © 2014 Marline L. Squance et al. All rights reserved. Effects of Glossopharyngeal Insufflation in Ankylosing Spondylitis: A Pilot Study Sun, 23 Nov 2014 08:01:16 +0000 In Ankylosing Spondylitis (AS), thoracic range of motion is often greatly limited. The objective of the study was to describe the effects of 12 weeks of Glossopharyngeal Insufflation (GI) training in patients with AS. Dynamic spirometry included vital capacity, forced expiratory volume, and peak expiratory flow. Thoracic and lumbar range of motion was assessed by tragus-to-wall distance, modified Schober test, and tape measure. Disease activity, activity limitation, and health perception were assessed using the BAS-Indices, and tension in the thoracic region during GI was assessed using the Borg CR-10 scale. Adherence to training was recorded in an activity log, along with any remarks on the training. Ten patients were recruited and six male patients fulfilled the study protocol. Three patients were able to learn GI by exceeding their maximal vital capacity with 5% using GI. A significant increase in thoracic range of motion both on costae IV and at the level of the xiphoid process was seen. Thus, patients with AS can practice GI, it is safe if maximal exertion is avoided, and patients with some mobility in the chest can increase their lung function substantially by performing GI during 12 weeks. Nina Brodin, Peter Lindholm, Claudia Lennartsson, and Malin Nygren-Bonnier Copyright © 2014 Nina Brodin et al. All rights reserved. Are There Clinical Differences in Limited Systemic Sclerosis according to Extension of Skin Involvement? Tue, 11 Nov 2014 00:00:00 +0000 Objectives. To examine the characteristics of our patients with limited systemic sclerosis (lSSc) for differences between Barnett Type 1 (sclerodactyly only) and Type 2 or intermediate (acrosclerosis-distal but may reach up to elbows and/or knees plus face) subsets. Methods. Records of patients between January 1, 2000, and December 31, 2011, with SSc or those with anti-Scl-70, anticentromere, or antinucleolar antibodies were reviewed. Only cases fulfilling ACR 1980 criteria were included and classified as diffuse or limited according to LeRoy’s criteria. Limited SSc was separated into sclerodactyly and acrosclerosis (Barnett’s Types 1 and 2). Results. 234 SSc patients (216 females) fulfilled criteria. Female/male ratio was 12 : 1; 24% had dSSc and 76% lSSC (64% Type 1 and 12% Type 2). Total follow-up was 688 patient-years. Within lSSC, the Type 2 group had significantly shorter duration of Raynaud’s and more anti-Scl-70 and less anticentromere antibodies. In particular, interstitial lung disease (ILD) was significantly more prevalent in Type 2 group and similar to Type 3. Conclusions. These results appear to confirm that extension of skin involvement within limited SSc may identify two different subsets with clinical and serologic characteristics. Marina Scolnik, Luis J. Catoggio, Eliana Lancioni, Mirtha R. Sabelli, Carla M. Saucedo, Josefina Marin, and Enrique R. Soriano Copyright © 2014 Marina Scolnik et al. All rights reserved. Risk of Type 2 Diabetes among Osteoarthritis Patients in a Prospective Longitudinal Study Tue, 04 Nov 2014 13:00:37 +0000 Objectives. Our aim was to determine the risk of diabetes among osteoarthritis (OA) cases in a prospective longitudinal study. Methods. Administrative health records of 577,601 randomly selected individuals from British Columbia, Canada, from 1991 to 2009, were analyzed. OA and diabetes cases were identified by checking physician’s visits and hospital records. From 1991 to 1996 we documented 19,143 existing OA cases and selected one non-OA individual matched by age, sex, and year of administrative records. Poisson regression and Cox proportional hazards models were fitted to estimate the effects after adjusting for available sociodemographic and medical factors. Results. At baseline, the mean age of OA cases was 61 years and 60.5% were women. Over 12 years of mean follow-up, the incidence rate (95% CI) of diabetes was 11.2 (10.90–11.50) per 1000 person years. Adjusted RRs (95% CI) for diabetes were 1.27 (1.15–1.41), 1.21 (1.08–1.35), 1.16 (1.04–1.28), and 0.99 (0.86–1.14) for younger women (age 20–64 years), older women (age ≥ 65 years), younger men, and older men, respectively. Conclusion. Younger adults and older women with OA have increased risks of developing diabetes compared to their age-sex matched non-OA counterparts. Further studies are needed to confirm these results and to elucidate the potential mechanisms. M. Mushfiqur Rahman, Jolanda Cibere, Aslam H. Anis, Charlie H. Goldsmith, and Jacek A. Kopec Copyright © 2014 M. Mushfiqur Rahman et al. All rights reserved. Clinical and Autoimmune Profile of Scleroderma Patients from Western India Sun, 19 Oct 2014 06:13:57 +0000 Background. Systemic sclerosis (SSc, scleroderma) is a disorder characterized by fibrosis of skin and visceral organs. Pathogenesis of scleroderma is complex and is incompletely understood as yet. Autoantibodies in SSc represent a serologic hallmark which have clinical relevance, with diagnostic and prognostic potential. Objectives. To study distribution of clinical manifestations and to identify frequency of autoantibodies among subtypes of scleroderma patients from Western India. Methodology. One hundred and ten scleroderma patients were clinically classified according to the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria. All these patients were in active stage of disease. Clinical manifestations were recorded at the time of presentation. Autoantibodies were tested in them by indirect immunofluorescence test and ELISA. Immunoglobulin levels were estimated by nephelometer. These parameters were further correlated with clinical presentation of the disease. Results. Scleroderma patients had M : F ratio of 1 : 10 where mean age at evaluation was years and a mean disease duration was months. Clinical subtypes showed that 45 patients (40.9%) had diffused cutaneous (dcSSc) lesions, 32 patients (29.1%) had limited cutaneous (lcSSc) lesions, and 33 patients (30%) had other autoimmune overlaps. The overall frequency of ANA in SSc patients studied was 85.5%. The frequency of anti-Scl70, anti-centromere, anti-endothelial cell antibodies (AECA), and anti-keratinocyte antibodies (AKA) was 62.7%, 22.7%, 30%, and 40.9%, respectively. Anti-Scl70 antibodies were significantly high (75.6% versus 46.9%) among dcSSc patients () whereas anti-centromere antibodies were significantly high (9% versus 38%) among lcSSc patients when these two subtypes were compared (). Conclusion. This study supports that there are geoepidemiological variations among scleroderma patients for their clinical presentation, autoantibody profile, and immune parameters across the country. Vandana Pradhan, Anjali Rajadhyaksha, Milind Nadkar, Pallavi Pandit, Prathamesh Surve, Maxime Lecerf, Jagadeesh Bayry, Srinivas Kaveri, and Kanjaksha Ghosh Copyright © 2014 Vandana Pradhan et al. All rights reserved.