Introduction Analyses of large clinical datasets from early arthritis cohorts permit the development of algorithms that may be used for outcome prediction in individual patients. The value added by routine use of musculoskeletal ultrasound (MSUS) in an early arthritis setting, as a component of such predictive algorithms, remains to be determined. Methods The authors undertook a retrospective analysis of a large, true-to-life, observational inception cohort of early arthritis patients in Newcastle upon Tyne, UK, which included patients with inflammatory arthralgia but no clinically swollen joints. A pragmatic, 10-minute MSUS assessment protocol was developed, and applied to each of these patients at baseline. Logistic regression was used to develop two "risk metrics" that predicted the development of a persistent inflammatory arthritis (PIA), with or without the inclusion of MSUS parameters. Results A total of 379 enrolled patients were assigned definitive diagnoses after ≥12 months follow-up (median 28 months), of whom 162 (42%) developed a persistent inflammatory arthritis. A risk metric derived from 12 baseline clinical and serological parameters alone had an excellent discriminatory utility with respect to an outcome of PIA (area under receiver operator characteristic (ROC) curve 0.91; 95% CI 0.88 to 0.94). The discriminatory utility of a similar metric, which incorporated MSUS parameters, was not significantly superior (area under ROC curve 0.91; 95% CI 0.89 to 0.94). Neither did this approach identify an added value of MSUS over the use of routine clinical parameters in an algorithm for discriminating PIA patients whose outcome diagnosis was rheumatoid arthritis (RA). Conclusions MSUS use as a routine component of assessment in an early arthritis clinic did not add substantial discriminatory value to a risk metric for predicting PIA. PMID:24028567
Choi, Ivy Y; Karpus, Olga N; Turner, Jason D; Hardie, Debbie; Marshall, Jennifer L; de Hair, Maria J H; Maijer, Karen I; Tak, Paul P; Raza, Karim; Hamann, Jörg; Buckley, Christopher D; Gerlag, Danielle M; Filer, Andrew
Previous studies have shown increased expression of stromal markers in synovial tissue (ST) of patients with established rheumatoid arthritis (RA). Here, ST expression of stromal markers in early arthritis in relationship to diagnosis and prognostic outcome was studied. ST from 56 patients included in two different early arthritis cohorts and 7 non-inflammatory controls was analysed using immunofluorescence to detect stromal markers CD55, CD248, fibroblast activation protein (FAP) and podoplanin. Diagnostic classification (gout, psoriatic arthritis, unclassified arthritis (UA), parvovirus associated arthritis, reactive arthritis and RA), disease outcome (resolving vs persistent) and clinical variables were determined at baseline and after follow-up, and related to the expression of stromal markers. We observed expression of all stromal markers in ST of early arthritis patients, independent of diagnosis or prognostic outcome. Synovial expression of FAP was significantly higher in patients developing early RA compared to other diagnostic groups and non-inflammatory controls. In RA FAP protein was expressed in both lining and sublining layers. Podoplanin expression was higher in all early inflammatory arthritis patients than controls, but did not differentiate diagnostic outcomes. Stromal marker expression was not associated with prognostic outcomes of disease persistence or resolution. There was no association with clinical or sonographic variables. Stromal cell markers CD55, CD248, FAP and podoplanin are expressed in ST in the earliest stage of arthritis. Baseline expression of FAP is higher in early synovitis patients who fulfil classification criteria for RA over time. These results suggest that significant fibroblast activation occurs in RA in the early window of disease.
Altawil, Reem; Saevarsdottir, Saedis; Wedrén, Sara; Alfredsson, Lars; Klareskog, Lars
Objective To investigate the frequency of remaining pain in early rheumatoid arthritis (RA) after 3 months of treatment with methotrexate as the only disease modifying antirheumatic drug, with a special focus on patients with a good clinical response. Methods The study base was cases reported to a population‐based early RA cohort who had followup data from the Swedish Rheumatology Quality Register (n = 1,241). The Disease Activity Score in 28 joints European League Against Rheumatism (EULAR) response criteria were used to evaluate clinical response to treatment as good, moderate, and no response. The primary end point was remaining pain at the 3‐months followup visit, defined as pain >20 mm on a 100‐mm visual analog scale (VAS). Results Remaining pain in spite of a EULAR good response at followup was associated with higher baseline disability, using the Health Assessment Questionnaire (adjusted odds ratio [OR] 2.2 [95% confidence interval (95% CI) 1.4–3.4] per unit increase), and less baseline inflammation, using the erythrocyte sedimentation rate (adjusted OR 0.81 [95% CI 0.70–0.93] per 10‐mm increase). Similar associations were detected for remaining pain at followup in spite of low inflammatory activity, defined as a C‐reactive protein level <10. Increase in VAS pain during the treatment period was observed in 19% of the whole cohort, with frequencies in the EULAR response groups of 9% (good response), 15% (moderate response), and 45% (no response). Conclusion These results are in line with the hypothesis that a subgroup of early RA patients exhibits pain that is not inflammatory mediated, where alternative treatment strategies to traditional antiinflammatory medications need to be considered. PMID:26784398
Norli, Ellen Sauar; Brinkmann, Gina H; Kvien, Tore K; Bjørneboe, Olav; Haugen, Anne J; Nygaard, Halvor; Thunem, Cathrine; Lie, Elisabeth; Mjaavatten, Maria D
To study occurrence of and factors associated with self-limiting arthritis among patients fulfilling the 2010 ACR/EULAR classification criteria for rheumatoid arthritis (RA) (2010 RA criteria) in patients with ≤16 weeks׳ duration of joint swelling. We applied the 2010 RA criteria in 1118 patients included in a 2-year longitudinal cohort. In all, 256 patients fulfilled the 2010 RA criteria at baseline; outcome was defined as either "self-limiting arthritis" (no DMARD use during follow-up, no swollen joints at last assessment, and no final clinical diagnosis of RA) or "persistent disease." The associations between baseline characteristics, including the components of the 2010 RA criteria score, and outcomes were studied. In total, 36 of 256 patients (14.1%) classified as having RA had self-limiting arthritis. These patients differed from patients with persistent disease according to ACPA positivity (11.1% vs. 65.0%, p < 0.001), duration of joint swelling (median = 47.5 vs. 66.0 days, p = 0.002), 2010 RA criteria points (median = 6.0 vs. 7.0, p < 0.001), and ever smoking (52.8% vs. 74.5%, p = 0.01). Having no serology points and no duration points were independent predictors of self-limiting arthritis. The rate of self-limiting arthritis was 2.7% vs. 29.4% among ACPA positive vs. ACPA negative patients (p < 0.001), and 32.5% when duration of joint swelling was <4 weeks vs. 10.6% with longer duration (p < 0.001). Negative ACPA status, short duration of joint swelling and being a never smoker were factors associated with self-limiting arthritis in early arthritis patients classified as having RA at presentation. Our findings contribute to identify patients who potentially do not need DMARDs and who should not be included in early RA clinical drug trials. Copyright © 2016 Elsevier Inc. All rights reserved.
Brinkmann, Gina H; Norli, Ellen S; Kvien, Tore K; Haugen, Anne J; Grøvle, Lars; Nygaard, Halvor; Bjørneboe, Olav; Thunem, Cathrine; Mjaavatten, Maria D; Lie, Elisabeth
To examine the 2-year disease course in patients with undifferentiated arthritis (UA) focusing on fulfillment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) rheumatoid arthritis (RA) classification criteria. Data were provided by the Norwegian Very Early Arthritis Clinic study, which included patients presenting with ≥ 1 swollen joint of ≤ 16 weeks' duration. UA was defined as patients not fulfilling the 2010 ACR/EULAR RA criteria and who did not have a clinical diagnosis other than RA at baseline. The main outcome was fulfillment of the 2010 RA criteria. Secondary outcomes were disease-modifying antirheumatic drug (DMARD) use, resolution of synovitis without use of DMARD during followup, and final clinical diagnosis. We included 477 patients with UA of whom 47 fulfilled the 2010 ACR/EULAR RA criteria during followup (UA-RA) and 430 did not (UA-non-RA). Of the UA-RA patients, 70% fulfilled the criteria within the first 6 months. UA-RA patients were older, more often positive for rheumatoid factor and anticitrullinated protein antibodies, female, and ever smokers, and they more often presented with polyarticular arthritis, small joint involvement, and a swollen shoulder joint. During followup, 53% of UA-RA patients vs 13% of UA-non-RA patients used DMARD (p < 0.001). Overall, 71% of patients with UA achieved absence of clinical synovitis at final followup without use of DMARD. The most frequent final clinical diagnosis was UA (61%). Only 9.8% of patients with UA fulfilled the 2010 RA criteria during 2-year followup. Small joint involvement and swollen shoulder joint were among the factors associated with RA development. In two-thirds of patients with UA, the arthritis resolved without use of DMARD.
Landewé, R B M; Geusens, P; van der Heijde, D M F M; Boers, M; van der Linden, S J; Garnero, P
Background Markers of collagen type I (CTX‐1) and type II (CTX‐II) degradation, reflecting bone and cartilage breakdown, appear to predict long term radiographic progression in chronic persistent arthritis. Objective To analyse longitudinally whether changes in arthritis severity are linked to immediate changes in the level of CTX‐I and CTX‐II degradation. Methods CTX‐I and CTX‐II were measured in urine samples from 105 patients with early rheumatoid arthritis who had participated in the COBRA trial at baseline and at 3, 6, 9, and 12 months after the start of treatment. The course of the biomarkers over time was compared with the course of ESR, swollen and tender joint counts, and 28 joint disease activity score (DAS28), measured at the same time points, with adjustment for rheumatoid factor, treatment, and baseline radiographic damage, by generalised estimating equations (GEE) with first order autoregression. Results GEE showed that CTX‐I was longitudinally associated with DAS28, but not with ESR, swollen joint count, or tender joint count. CTX‐II, however, was longitudinally associated with ESR, swollen joint count and DAS28, but not with tender joint count. The longitudinal association implies that an increase in the extent of arthritis is immediately followed by an increase in collagen type II degradation, and to a lesser extent collagen type I degradation. Conclusions Cartilage degradation as measured by CTX‐II and to a lesser extent bone degradation as measured by CTX‐I closely follows indices of arthritis. Clinically perceptible arthritis is responsible for immediate damage, which will become visible on plain x rays only much later. PMID:16126801
Ramagli, Alicia; Corbacho, Inés; Linhares, Fernanda; de Abreu, Paloma; Teijeiro, Raquel; Garau, Mariela; Dapueto, Juan
While many studies have tried to show that early intervention improves the clinical outcomes of early-onset arthritis, only a few were carried out in Latin America. The aim of this study was to describe the Pan-American Registry of Early-Onset Arthritis (REPANARC) project and report the preliminary outcomes of a cohort of patients. The REPANARC cohort consisted of a sample of patients from 6 Latin American countries. Patients with arthritis of 1 or more joints of 1-year duration or less were assessed by a rheumatologist during 6 consecutive clinical visits for a follow-up period of 2 years. The registry included clinical characteristics, medical history, physical examination, disease activity, analytical chemistries, imaging, current treatment, and a set of patient-reported outcome measures evaluating disability, psychological distress, and quality of life. A total of 173 patients were included with mean age of 41.9 ± 13.2 years; 83.8% were women. The predominant presentations at onset were insidious, polyarticular, additive, bilateral, and symmetrical. The initial diagnoses were rheumatoid arthritis (50.6%), undifferentiated arthritis (40.5%), and other arthritis (8.9%). With Disease Activity Score in 28 Joints, 76.9% had moderate to high disease activity, and 61.9% had moderate to severe disability (Health Assessment Questionnaire). Considering undifferentiated arthritis, 60.3% persisted undifferentiated, 29.4% evolved as rheumatoid arthritis, 4.4% remained self-limited, and 5.9% to other forms. The frequencies of depression and anxiety were high as measured with the Hospital Anxiety and Depression Scale, and approximately 20% had significant decrements in quality of life measured with the Medical Outcomes Study Short-Form 36 Health Survey Version 2. Mean time from the first symptoms to the first visit to a rheumatologist was 126 days. Shorter delays were confirmed to be associated with better outcomes. The REPANARC project is a useful tool to provide valuable
Turk, Samina A; Heslinga, Sjoerd C; Dekker, Jill; Britsemmer, Linda; van der Lugt, Véronique; Lems, Willem F; van Schaardenburg, Dirkjan; Nurmohamed, Michael T
To investigate the prevalence of conduction disorders in patients with early arthritis and the relationship with inflammation and traditional cardiovascular (CV) risk factors. Patients with rheumatoid arthritis (RA) have a 2-fold higher risk of sudden cardiac death, possibly owing to conduction disorders. This increased risk might already be present at the clinical onset of arthritis. Therefore, we assessed electrocardiography, blood pressure, 28-joint Disease Activity Score (DAS28), lipid profile, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level in 480 patients with early arthritis at baseline and after 1 year. The prevalence of conduction disorders was 12.5%. Conduction times at baseline were not associated with DAS28, ESR, or CRP levels and did not change during antirheumatic treatment. Baseline and the improvement in DAS28 (European League Against Rheumatism response), ESR, and CRP were significantly associated with heart rate, lipid profile, and blood pressure. Elevated total cholesterol and blood pressure were associated with an increased QRS time. The change in heart rate differed 7.3 bpm between patients with the least versus largest DAS improvement. The prevalence of conduction disorders in patients with early arthritis was 12.5%, which is similar to the general population and was not associated with changes in inflammation markers. However, a high cholesterol was associated with a prolonged QRS time. Therefore, the emphasis of CV risk management in arthritis should not be only on treatment of disease activity but also on traditional CV risk factors. The relationship between the improvement in disease activity and heart rate is remarkable because this could imply a 10-year CV mortality risk difference of 24%.
Stomp, Wouter; Krabben, Annemarie; van der Heijde, Désirée; Huizinga, Tom W J; Bloem, Johan L; van der Helm-van Mil, Annette H M; Reijnierse, Monique
Magnetic resonance imaging (MRI) is increasingly used in rheumatoid arthritis (RA) research. A European League Against Rheumatism (EULAR) task force recently suggested that MRI can improve the certainty of RA diagnosis. Because this recommendation may reflect a tendency to use MRI in daily practice, thorough studies on the value of MRI are required. Thus far no large studies have evaluated the accuracy of MRI to differentiate early RA from other patients with early arthritis. We performed a large cross-sectional study to determine whether patients who are clinically classified with RA differ in MRI features compared to patients with other diagnoses. In our study, 179 patients presenting with early arthritis (median symptom duration 15.4 weeks) underwent 1.5T extremity MRI of unilateral wrist, metacarpophalangeal, and metatarsophalangeal joints according to our arthritis protocol, the foot without contrast. Images were scored according to OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) by 2 independent readers. Tenosynovitis was also assessed. The main outcome was fulfilling the 1987 American College of Rheumatology (ACR) criteria for RA. Test characteristics and areas under the receiver-operator-characteristic curves (AUC) were evaluated. In subanalyses, the 2010 ACR/EULAR criteria were used as outcome, and analyses were stratified for anticitrullinated protein antibodies (ACPA). The ACR 1987 criteria were fulfilled in 43 patients (24.0%). Patients with RA had higher scores for synovitis, tenosynovitis, and bone marrow edema (BME) than patients without RA (p < 0.05). ACPA-positive patients had more BME (median scores 6.5 vs. 4.25, p = 0.016) than ACPA-negative patients. For all MRI features, the predictive value for the presence of RA was low (< 50%). For all MRI features the AUC were < 0.70. Patients who fulfilled ACR/EULAR 2010 criteria but not ACR87 criteria for RA had less synovitis than patients who were positive for RA according to
Goldbach-Mansky, R; Suson, S; Wesley, R; Hack, C; El-Gabalawy, H; Tak, P
Background: Raised granzyme B in serum and synovium of patients with rheumatoid arthritis suggests a role for cytotoxic T cells and natural killer cells in the pathogenesis of this disease. Objective: To evaluate serum granzyme B in patients with early arthritis and correlate it with specific diagnosis and clinical indices of disease severity. Methods: 257 patients with inflammatory arthritis for less than one year (46% rheumatoid arthritis, 17% spondyloarthropathy, 37% undifferentiated arthritis) had a prospective clinical, serological, and radiographic evaluation. Granzyme B was measured in initial sera by ELISA. Patients were HLA typed for DR alleles using sequence specific primers. A logistic regression model was used to evaluate the potential prognostic value of serum granzyme B in predicting radiographic erosions after one year of follow up. Results: Granzyme B values were similar in rheumatoid arthritis, spondyloarthropathy, and undifferentiated arthritis. Concentrations were higher in rheumatoid factor (RF) positive patients than in RF negative patients (mean (SD): 3.15 (0.92) v 2.89 (0.71) pg/ml; p<0.05). After one year, erosions were present in 30% of patients in the overall cohort, and in 44% of patients with rheumatoid arthritis. In the entire cohort, serum granzyme B did not predict erosions independently. However, high granzyme B was an independent predictor of early erosions in patients with RF positive rheumatoid arthritis (odds ratio = 4.83 (95% confidence interval, 1.13 to 20.59)) (p<0.05). Conclusions: Granzyme B may be a useful prognostic marker in early rheumatoid arthritis and may provide important clues to the pathogenesis of this disease. PMID:15471892
I, González-Álvaro; A.M, Ortiz; I.V, Seoane; R, García-Vicuña; C, Martínez; R.P, Gomariz
The heterogeneous nature of rheumatoid arthritis (RA) complicates early recognition and treatment. In recent years, a growing body of evidence has demonstrated that intervention during the window of opportunity can improve the response to treatment and slow—or even stop—irreversible structural changes. Advances in therapy, such as biologic agents, and changing approaches to the disease, such as the treat to target and tight control strategies, have led to better outcomes resulting from personalized treatment to patients with different prognostic markers. The various biomarkers identified either facilitate early diagnosis or make it possible to adjust management to disease activity or poor outcomes. However, no single biomarker can bridge the gap between disease onset and prescription of the first DMARD, and traditional biomarkers do not identify all patients requiring early aggressive treatment. Furthermore, the outcomes of early arthritis cohorts are largely biased by the treatment prescribed to patients; therefore, new challenges arise in the search for prognostic biomarkers. Herein, we discuss the value of traditional and new biomarkers and suggest the need for intensive treatment as a new surrogate marker of poor prognosis that can guide therapeutic decisions in the early stages of RA. PMID:25163741
Mauermann, Maria; Hochauf-Stange, Kristina; Kleymann, Alexander; Conrad, Karsten; Aringer, Martin
To analyse the subgroup of early arthritis patients with new onset parvovirus infections for details that may help narrow the population tested. From their routine patient charts, patient histories and clinical and serological data were obtained for all 130 patients of the Rheumatology division with parvovirus serology performed. 11 patients had acute parvovirus infections, defined by specific IgM antibodies. 95 patients had a previous infection, 16 were never infected, together forming the n=111 control group, and 8 patients had to be excluded. Most patients with acute parvovirus infection had an acute onset, highly symmetrical polyarthritis of small joints, which was preceded by prodromal symptoms. Positive ANA were frequently found, whereas C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were only mildly elevated. No frank synovitis was found longer than two weeks after disease onset. Most patients were free of symptoms within three months, and no patient in the parvovirus group developed rheumatoid arthritis or a connective tissue disease. Parvovirus serology may be helpful in patients with acute polyarthritis of very recent onset, and if they give a history of prodromal symptoms, in particular. In most instances, parvovirus arthritis is an acute disease, which is rapidly self-limiting.
Non-pharmacological and pharmacological interventions in patients with early arthritis: a systematic literature review informing the 2016 update of EULAR recommendations for the management of early arthritis
DAIEN, Claire Immediato; HUA, Charlotte; COMBE, Bernard; LANDEWE, Robert
Objective To perform a systematic literature review (SLR) on pharmacological and non-pharmacological treatments, in order to inform the European League Against Rheumatism (EULAR) recommendations for the management of early arthritis (EA). Methods The expert committee defined research questions concerning non-pharmacological interventions, patient information and education, non-steroidal anti-inflammatory drug, glucocorticoid (GC) and disease-modifying antirheumatic drugs (DMARDs) use, as well as on disease monitoring. The SLR included articles published after the last EULAR SLR until November 2015 found in the MEDLINE, EMBASE and Cochrane databases and abstracts from the 2014 and 2015 American College of Rheumatology and EULAR conferences. Results Exercise programmes may improve pain and physical function in patients with EA. Patients with EA treated within the first 3 months of symptoms have better clinical and radiological outcomes than those treated beyond 3 months. The clinical and radiological efficacy of GCs is confirmed, with similar efficacy of oral and parenteral administrations. Long-term data raise concerns regarding cardiovascular safety when using GCs. Step-up DMARD therapy is as effective as intensive DMARD therapy ‘ab initio’ for the long-term outcome of EA. Short-term superiority of intensive therapy with bDMARDs is not maintained on withdrawal of bDMARD. Patients with early psoriatic arthritis have better skin and joint outcomes when tight control is used compared to standard care. Conclusions The findings confirm the beneficial effect of exercise programmes and the importance of early drug therapy and tight control. They support the use of methotrexate and GCs as first-line drugs, although the long-term use of GCs raises safety concerns. PMID:28151539
Non-pharmacological and pharmacological interventions in patients with early arthritis: a systematic literature review informing the 2016 update of EULAR recommendations for the management of early arthritis.
Daien, Claire Immediato; Hua, Charlotte; Combe, Bernard; Landewe, Robert
To perform a systematic literature review (SLR) on pharmacological and non-pharmacological treatments, in order to inform the European League Against Rheumatism (EULAR) recommendations for the management of early arthritis (EA). The expert committee defined research questions concerning non-pharmacological interventions, patient information and education, non-steroidal anti-inflammatory drug, glucocorticoid (GC) and disease-modifying antirheumatic drugs (DMARDs) use, as well as on disease monitoring. The SLR included articles published after the last EULAR SLR until November 2015 found in the MEDLINE, EMBASE and Cochrane databases and abstracts from the 2014 and 2015 American College of Rheumatology and EULAR conferences. Exercise programmes may improve pain and physical function in patients with EA. Patients with EA treated within the first 3 months of symptoms have better clinical and radiological outcomes than those treated beyond 3 months. The clinical and radiological efficacy of GCs is confirmed, with similar efficacy of oral and parenteral administrations. Long-term data raise concerns regarding cardiovascular safety when using GCs. Step-up DMARD therapy is as effective as intensive DMARD therapy 'ab initio' for the long-term outcome of EA. Short-term superiority of intensive therapy with bDMARDs is not maintained on withdrawal of bDMARD. Patients with early psoriatic arthritis have better skin and joint outcomes when tight control is used compared to standard care. The findings confirm the beneficial effect of exercise programmes and the importance of early drug therapy and tight control. They support the use of methotrexate and GCs as first-line drugs, although the long-term use of GCs raises safety concerns.
Ledingham, Joanna M; Snowden, Neil; Rivett, Ali; Galloway, James; Ide, Zoe; Firth, Jill; MacPhie, Elizabeth; Kandala, Ngianga; Dennison, Elaine M; Rowe, Ian
A national audit was performed assessing the early management of suspected inflammatory arthritis by English and Welsh rheumatology units. The aim of this audit was to measure the performance of rheumatology services against National Institute for Health and Care Excellence (NICE) quality standards (QSs) for the management of early inflammatory arthritis benchmarked to regional and national comparators for the first time in the UK. All individuals >16 years of age presenting to rheumatology services in England and Wales with suspected new-onset inflammatory arthritis were included in the audit. Information was collected against six NICE QSs that pertain to early inflammatory arthritis management. We present national data for the 6354 patients recruited from 1 February 2014 to 31 January 2015; 97% of trusts and health boards in England and Wales participated in this audit. Only 17% of patients were referred by their general practitioner within 3 days of first presentation. Specialist rheumatology assessment occurred within 3 weeks of referral in 38% of patients. The target of DMARD initiation within 6 weeks of referral was achieved in 53% of RA patients; 36% were treated with combination DMARDs and 82% with steroids within the first 3 months of specialist care. Fifty-nine per cent of patients received structured education on their arthritis within 1 month of diagnosis. In total, 91% of patients had a treatment target set; the agreed target was achieved within 3 months of specialist review in only 27% of patients. Access to urgent advice via a telephone helpline was reported to be available in 96% of trusts. The audit has highlighted gaps between NICE standards and delivery of care, as well as substantial geographic variability. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: email@example.com.
García-Gavín, J; Pérez-Pérez, L; Tinazzi, I; Vidal, D; McGonagle, D
The Early Arthritis for Psoriatic patients (EARP) questionnaire is a screening tool for psoriatic arthritis with good measuring properties in its original Italian version but has not been culturally adapted to Spanish. This article presents the adaptation for Spanish population, prior to validation step. Application of the methodology recommended by the International Society Pharmacoeconomic and Outcome Research for cultural adaptations of measures focused on the patient and comprising the steps of: preparation, translation, reconciliation, back translation and review, harmonization, cognitive debriefing and review, proofreading. In preparing, the permission of the authors of the original questionnaire for cultural adaptation was obtained and they worked as a consultant during the process. The translation of the original questionnaire into Spanish was made by native translators who made minor modifications accepted by the authors of the original version. The back-translation into Italian was performed, obtaining an equivalent to the original EARP version. The Spanish version of the back-translation was answered by 35 patients in a cognitive debriefing. They answered all items without making additional contributions. The cultural adaptation of the questionnaire EARP for Spanish population is the first step for later use in routine clinical practice. The standardized methodology ensures the equivalence between the EARP in Spanish and the original one. In a second step, validation will take place in Spanish population. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.
Fleischmann, Roy M; Huizinga, Tom W J; Kavanaugh, Arthur F; Wilkinson, Bethanie; Kwok, Kenneth; DeMasi, Ryan; van Vollenhoven, Ronald F
Introduction Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24 months in methotrexate (MTX)-naive adult patients with RA. In this post hoc analysis, we compared efficacy and safety of tofacitinib in patients with early (disease duration <1 year) versus established (≥1 year) RA. Methods MTX-naive patients ≥18 years with active RA received tofacitinib monotherapy (5 or 10 mg two times a day, or MTX monotherapy, in a 24-month Phase 3 trial. Results Of 956 patients (tofacitinib 5 mg two times a day, n=373; tofacitinib 10 mg two times a day, n=397; MTX, n=186), 54% had early RA. Baseline disease activity and functional disability were similar in both groups; radiographic damage was greater in patients with established RA. At month 24, clinical response rates were significantly greater in patients with early versus established RA in the tofacitinib 5 mg two times a day group. Both tofacitinib doses had greater effects on clinical, functional and radiographic improvements at 1 and 2 years compared with MTX, independent of disease duration. No new safety signals were observed. Conclusions Treatment response was generally similar in early and established RA; significantly greater improvements were observed at month 24 with tofacitinib 5 mg two times a day in early versus established RA. Tofacitinib 5 and 10 mg two times a day demonstrated greater efficacy versus MTX irrespective of disease duration. No difference in safety profiles was observed between patients with early or established RA. Trial registration number NCT01039688; Results. PMID:27493790
Fleischmann, Roy M; Huizinga, Tom W J; Kavanaugh, Arthur F; Wilkinson, Bethanie; Kwok, Kenneth; DeMasi, Ryan; van Vollenhoven, Ronald F
Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24 months in methotrexate (MTX)-naive adult patients with RA. In this post hoc analysis, we compared efficacy and safety of tofacitinib in patients with early (disease duration <1 year) versus established (≥1 year) RA. MTX-naive patients ≥18 years with active RA received tofacitinib monotherapy (5 or 10 mg two times a day, or MTX monotherapy, in a 24-month Phase 3 trial. Of 956 patients (tofacitinib 5 mg two times a day, n=373; tofacitinib 10 mg two times a day, n=397; MTX, n=186), 54% had early RA. Baseline disease activity and functional disability were similar in both groups; radiographic damage was greater in patients with established RA. At month 24, clinical response rates were significantly greater in patients with early versus established RA in the tofacitinib 5 mg two times a day group. Both tofacitinib doses had greater effects on clinical, functional and radiographic improvements at 1 and 2 years compared with MTX, independent of disease duration. No new safety signals were observed. Treatment response was generally similar in early and established RA; significantly greater improvements were observed at month 24 with tofacitinib 5 mg two times a day in early versus established RA. Tofacitinib 5 and 10 mg two times a day demonstrated greater efficacy versus MTX irrespective of disease duration. No difference in safety profiles was observed between patients with early or established RA. NCT01039688; Results.
Ledingham, Joanna M; Snowden, Neil; Rivett, Ali; Galloway, James; Ide, Zoe; Firth, Jill; MacPhie, Elizabeth; Kandala, Ngianga; Dennison, Elaine M; Rowe, Ian
Our aim was to conduct a national audit assessing the impact and experience of early management of inflammatory arthritis by English and Welsh rheumatology units. The audit enables rheumatology services to measure for the first time their performance, patient outcomes and experience, benchmarked to regional and national comparators. All individuals >16 years of age presenting to English and Welsh rheumatology services with suspected new-onset inflammatory arthritis were included in the audit. Clinician- and patient-derived outcome and patient-reported experience measures were collected. Data are presented for the 6354 patients recruited from 1 February 2014 to 31 January 2015. Ninety-seven per cent of English and Welsh trusts participated. At the first specialist assessment, the 28-joint DAS (DAS28) was calculated for 2659 (91%) RA patients [mean DAS28 was 5.0 and mean Rheumatoid Arthritis Impact of Disease (RAID) score was 5.6]. After 3 months of specialist care, the mean DAS28 was 3.5 and slightly >60% achieved a meaningful DAS28 reduction. The average RAID score and reduction in RAID score were 3.6 and 2.4, respectively. Of the working patients ages 16-65 years providing data, 7, 5, 16 and 37% reported that they were unable to work, needed frequent time off work, occasionally and rarely needed time off work due to their arthritis, respectively; only 42% reported being asked about their work. Seventy-eight per cent of RA patients providing data agreed with the statement 'Overall in the last 3 months I have had a good experience of care for my arthritis'; <2% disagreed. This audit demonstrates that most RA patients have severe disease at the time of presentation to rheumatology services and that a significant number continue to have high disease activity after 3 months of specialist care. There is a clear need for the National Health Service to develop better systems for capturing, coding and integrating information from outpatient clinics, including measures of
González-Álvaro, Isidoro; Ortiz, Ana M.; Alvaro-Gracia, José María; Castañeda, Santos; Díaz-Sánchez, Belen; Carvajal, Inmaculada; García-Vadillo, J. Alberto; Humbría, Alicia; López-Bote, J. Pedro; Patiño, Esther; Tomero, Eva G.; Vicente, Esther F.; Sabando, Pedro; García-Vicuña, Rosario
Background Interleukin-15 (IL-15) is thought to be involved in the physiopathological mechanisms of RA and it can be detected in the serum and the synovial fluid of inflamed joints in patients with RA but not in patients with osteoarthritis or other inflammatory joint diseases. Therefore, the objective of this work is to analyse whether serum IL-15 (sIL-15) levels serve as a biomarker of disease severity in patients with early arthritis (EA). Methodology and Results Data from 190 patients in an EA register were analysed (77.2% female; median age 53 years; 6-month median disease duration at entry). Clinical and treatment information was recorded systematically, especially the prescription of disease modifying anti-rheumatic drugs. Two multivariate longitudinal analyses were performed with different dependent variables: 1) DAS28 and 2) a variable reflecting intensive treatment. Both included sIL-15 as predictive variable and other variables associated with disease severity, including rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA). Of the 171 patients (638 visits analysed) completing the follow-up, 71% suffered rheumatoid arthritis and 29% were considered as undifferentiated arthritis. Elevated sIL-15 was detected in 29% of this population and this biomarker did not overlap extensively with RF or ACPA. High sIL-15 levels (β Coefficient [95% confidence interval]: 0.12 [0.06–0.18]; p<0.001) or ACPA (0.34 [0.01–0.67]; p = 0.044) were significantly and independently associated with a higher DAS28 during follow-up, after adjusting for confounding variables such as gender, age and treatment. In addition, those patients with elevated sIL-15 had a significantly higher risk of receiving intensive treatment (RR 1.78, 95% confidence interval 1.18–2.7; p = 0.007). Conclusions Patients with EA displaying high baseline sIL-15 suffered a more severe disease and received more intensive treatment. Thus, sIL-15 may be a biomarker for
Moura, Rita A; Canhão, Helena; Polido-Pereira, Joaquim; Rodrigues, Ana M; Navalho, Márcio; Mourão, Ana F; Resende, Catarina; Campanilho-Marques, Raquel; Madruga Dias, João; da Silva, José Alberto Pereira; Graca, Luis; Fonseca, João E
B cells play important roles in rheumatoid arthritis (RA). Given the beneficial effect of B cell depletion therapy in RA as well as the observed alterations in B cell subpopulations in this disease, we evaluated whether changes in the expression of genes related to B cell survival and activation were already present in patients with untreated very early RA (VERA; < 6 weeks of disease duration). The expression of a group of B cell-related activation and survival genes was quantified in peripheral blood mononuclear cells from patients with VERA by real-time PCR and compared with untreated early RA (< 1 year), established treated RA, and other untreated early arthritis conditions. Serum B cell-activating factor belonging to the tumor necrosis factor family (BAFF) was quantified by ELISA. BAFF gene expression and serum levels were highest in patients with VERA. The expression of BAFF receptor (BAFF-R) increased with disease progression, while transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) was elevated since the first weeks of RA onset. Paired box 5 gene expression was also increased at all RA stages. Chemokine (C-X-C motif) receptor 5 was elevated only in established RA. No differences were observed in B cell maturation antigen, activation-induced cytidine deaminase, B lymphocyte-induced maturation protein, and B cell lymphoma 2 expression. Disturbances in the expression of B cell-related activation and survival genes, particularly BAFF and TACI, occur from the onset of RA and precede changes in BAFF-R. These alterations can lead to the development of autoreactive B cells from the first weeks of RA onset.
Bøyesen, Pernille; Haavardsholm, Espen A; van der Heijde, Désirée; Østergaard, Mikkel; Hammer, Hilde Berner; Sesseng, Sølve; Kvien, Tore K
To examine the associations between modern imaging modalities and joint damage measured as 1-year MRI erosive progression, in early rheumatoid arthritis (RA) patients. 84 RA patients with disease duration of less than 1 year were included in this inception cohort. Patients were evaluated at baseline, 3, 6 and 12 months by core measures of disease activity, MRI and ultrasound grey-scale (USGS) of inflammation, conventional radiography and digital x-ray radiogrammetry (DXR) bone mineral density (BMD) of cortical hand bone. 53 of the 79 patients (67%) who completed the follow-up had MRI erosive progression (dependent variable). USGS and MRI bone marrow oedema (BME) were in multivariate analyses independent predictors of 1-year MRI erosive progression. There was a trend towards higher MRI synovitis score and 3-month DXR BMD loss in patients developing MRI erosions. On an individual level, USGS inflammation, MRI synovitis and MRI BME also somewhat better predicted outcome than rheumatoid factor, anticitrullinated protein antibodies and disease activity score 28. USGS inflammation and MRI BME were independent predictors of MRI erosive progression in early RA patients on a group level. The exact prognosis of the individual patients could not be determined by imaging alone.
Introduction Prior studies have demonstrated an increased frequency of antibodies to Porphyromonas gingivalis (Pg), a leading agent of periodontal disease, in rheumatoid arthritis (RA) patients. However, these patients generally had long-standing disease, and clinical associations with these antibodies were inconsistent. Our goal was to examine Pg antibody responses and their clinical associations in patients with early RA prior to and after disease-modifying antirheumatic drug (DMARD) therapy. Methods Serum samples from 50 DMARD-naïve RA patients were tested using an enzyme-linked immunosorbent assay with whole-Pg sonicate. For comparison, serum samples were tested from patients with late RA, patients with other connective tissue diseases (CTDs), age-similar healthy hospital personnel and blood bank donors. Pg antibody responses in early RA patients were correlated with standard RA biomarkers, measures of disease activity and function. Results At the time of enrollment, 17 (34%) of the 50 patients with early RA had positive immunoglobulin G (IgG) antibody responses to Pg, as did 13 (30%) of the 43 patients with late RA. RA patients had significantly higher Pg antibody responses than healthy hospital personnel and blood bank donors (P < 0.0001). Additionally, RA patients tended to have higher Pg antibody reactivity than patients with other CTDs (P = 0.1), and CTD patients tended to have higher Pg responses than healthy participants (P = 0.07). Compared with Pg antibody-negative patients, early RA patients with positive Pg responses more often had anti-cyclic citrullinated peptide (anti-CCP) antibody reactivity, their anti-CCP levels were significantly higher (P = 0.03) and the levels of anti-Pg antibodies correlated directly with anti-CCP levels (P < 0.01). Furthermore, at the time of study entry, the Pg-positive antibody group had greater rheumatoid factor values (P = 0.04) and higher inflammatory markers (erythrocyte sedimentation rate, or ESR) (P = 0.05), and
Deo, Sudha S; Shetty, Rashmi R; Mistry, Kejal J; Chogle, Arun R
Aim: Study was undertaken to analyze the frequency of anti-viral citrullinated peptide (anti-VCP) antibodies in sera from patients with early rheumatoid arthritis (ERA). Materials and Methods: Viral citrullinated peptide (VCP) and Epstein-Barr nuclear antigen (EBNA-1) peptide were commercially prepared and antibodies to these were determined in 25 patients of ERA, 40 disease control patients constituting 25 rheumatoid arthritis (RA), 7 systemic lupus erythematosus (SLE), 2 scleroderma, 1 spondyloarthritis (SpA), 1 juvenile rheumatoid arthritis (JRA), 1 osteoarthritis (OA), 1 psoriatic arthritis (PsA), 1 undifferentiated arthritis (UA), and 1 gout and 25 healthy controls (HCs) were taken for comparison. In-house ELISA was established for both the antibodies while cyclic citrullinated peptide (CCP) antibody was detected by commercial ELISA kit. Results: Significant increase in VCP antibody by ERA and disease controls than healthy normal was observed. VCP IgM antibody was significantly increased in RA patients than HC. The presence of VCP antibody signifies a good marker for ERA. We observed significant difference in the VCP IgG and IgM antibody when compared to EBNA-1. In-house ELISA established for EBNA-1 and VCP antibodies showed low sensitivity but 96% specificity. Conclusions: We observed that sera from early RA patients reacted to the deiminated protein encoded by Epstain Barr Virus (EBV). Thus a possible role of virus in inducing an anti-citrullinated peptide antibody (ACPA) response reveals viral etiology in this disease. PMID:21346905
Guseva, I A; Demidova, N V; Soroka, N E; Novikov, A A; Luchikhina, E L; Aleksandrova, E N; Lukina, G V; Fedorenko, E V; Aronova, E S; Samarkina, E Iu; Boldyreva, M N; Trofimov, D Iu; Karateev, D E; Nasonov, E L
The study is aimed to investigate the distribution of alleles of HLA-DRB1 gene in patients with early rheumatoid arthritis and healthy individuals in Russian population, and evaluate their significance as molecular genetic markers of rheumatoid arthritis predisposition and protection. The association between alleles of HLA-DRB1 genes, antibodies to cyclic citrullinated peptides and IgM rheumatoid factor was also studied. Low and high resolution HLA-DRB1 genotyping were compared. In the cohort of patients with early rheumatoid arthritis, the alleles of HLA-DRB1 gene were found to be markers of rheumatoid arthritis protection/risk, especially in the homozygous state. They determined production of antibodies to cyclic citrullinated peptides but were not associated with rheumatoid factor IgM levels. These findings support different autoimmune mechanisms of rheumatoid arthritis pathogenesis.
Meyfroidt, Sabrina; Van der Elst, Kristien; De Cock, Diederik; Joly, Johan; Westhovens, René; Hulscher, Marlies; Verschueren, Patrick
To investigate patients' experiences with intensive combination-treatment strategies with glucocorticoids (ICTS-GCs) in the early phase of early rheumatoid arthritis (ERA) treatment. We interviewed 26 participants individually, 4-6 months after initiation of ICTS-GCs (t1). Fourteen participants from the same sample took part in one of three focus groups at least 1 year after treatment initiation (t2). Each interview was audio-recorded, literally transcribed and thematically coded. The participants described concerns and feelings about ICTS-GCs that changed over time; for example, a fear of side effects diminished when the treatment effects were beneficial or expected side effects did not materialize. Moreover, participants indicated additional information needs at t1 and t2. The most used sources of information were healthcare professionals, relatives, and the Internet. Furthermore, participants reported on their relationship with healthcare professionals and the need for trust and reassurance, especially at t1. Lastly, participants described their personal self-management strategies. Despite their concerns at treatment initiation, most participants had positive experiences with ICTS-GCs. Healthcare professionals should be aware that, in the early phase of treatment, they can address patients' concerns, they are the most important information source, they need to create a relationship of trust, and guide patients in self-management strategies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Arts, E E A; Popa, C; Den Broeder, A A; Semb, A G; Toms, T; Kitas, G D; van Riel, P L; Fransen, J
This study was undertaken to assess the predictive ability of 4 established cardiovascular (CV) risk models for the 10-year risk of fatal and non-fatal CV diseases in European patients with rheumatoid arthritis. Prospectively collected data from the Nijmegen early rheumatoid arthritis (RA) inception cohort was used. Discriminatory ability for CV risk prediction was estimated by the area under the receiver operating characteristic curve. Calibration was assessed by comparing the observed versus expected number of events using Hosmer-Lemeshov tests and calibration plots. Sensitivity and specificity were calculated for the cut-off values of 10% and 20% predicted risk. Areas under the receiver operating characteristic curve were 0.78-0.80, indicating moderate to good discrimination between patients with and without a CV event. The CV risk models Systematic Coronary Risk Evaluation (SCORE), Framingham risk score (FRS) and Reynolds risk score (RRS) primarily underestimated CV risk at low and middle observed risk levels, and mostly overestimated CV risk at higher observed risk levels. The QRisk II primarily overestimated observed CV risk. For the 10% and 20% cut-off values used as indicators for CV preventive treatment, sensitivity ranged from 68-87% and 40-65%, respectively and specificity ranged from 55-76% and 77-88%, respectively. Depending on the model, up to 32% of observed CV events occurred in patients with RA who were classified as low risk (<10%) for CV disease. Established risk models generally underestimate (Systematic Coronary Risk Evaluation score, Framingham Risk Score, Reynolds risk score) or overestimate (QRisk II) CV risk in patients with RA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Albrecht, Katinka; Callhoff, Johanna; Buttgereit, Frank; Straub, Rainer H; Westhoff, Gisela; Zink, Angela
To evaluate the association between exposure to oral contraceptives (OCs) and clinical outcomes in an early arthritis cohort. Female patients with early inflammatory arthritis, ages 18-60 years, who were enrolled in an early arthritis cohort and had no exposure to hormone replacement were studied (n = 273). Associations between OC exposure (current/past/never) and disease activity, treatment, and patient-reported outcomes, including the Rheumatoid Arthritis Impact of Disease Score (RAID), the Rheumatoid Arthritis Disease Activity Index (RADAI), the Profile of Mood and Discomfort (PROFAD), and the Hannover Functional Assessment (FFbH), were studied over 2 years. Linear mixed models adjusted for age, body mass index, parity, smoking, and education were used. Eighteen percent of patients had never used OCs, 63% had used OCs in the past, and 19% currently used OCs. After adjustment, the current/past OC use was associated with better RAID, PROFAD, RADAI, and FFbH scores at 12 months (P < 0.05 for all) compared to never use. Longitudinally over 2 years, the mean RAID scores were significantly better in women with current/past OC use (P < 0.001). Actual inflammatory markers were not associated with OC use. Glucocorticoids were used by a higher percentage of OC never users than by current/past users (P = 0.08), especially in patients with impaired function (FFbH <70: odds ratio 4.2 [95% confidence interval 1.6-11]). For past as well as current use, OCs seem to moderate patient-reported outcomes in inflammatory arthritis. Protective effects may be induced via central nervous pathways rather than through the suppression of peripheral inflammation. © 2016, American College of Rheumatology.
Association of Anti-Porphyromonas gingivalis Antibody Titers With Nonsmoking Status in Early Rheumatoid Arthritis: Results From the Prospective French Cohort of Patients With Early Rheumatoid Arthritis.
Seror, Raphaèle; Le Gall-David, Sandrine; Bonnaure-Mallet, Martine; Schaeverbeke, Thierry; Cantagrel, Alain; Minet, Jacques; Gottenberg, Jacques-Eric; Chanson, Philippe; Ravaud, Philippe; Mariette, Xavier
To investigate the possible link between Porphyromonas gingivalis infection and rheumatoid arthritis (RA), according to antibody profile, genetic and environmental factors, and RA severity. For assessing P gingivalis infection, serum levels of antibodies directed against P gingivalis lipopolysaccharide were measured in 694 patients with early RA who were not exposed to steroids or disease-modifying antirheumatic drugs. Anti-P gingivalis antibody titers were compared between patients with early RA and various control groups, and according to various patient characteristics. Anti-P gingivalis antibody titers did not significantly differ between patients with RA and controls and did not significantly differ with anti-citrullinated protein antibody (ACPA), rheumatoid factor (RF), or HLA shared epitope status. Anti-P gingivalis antibody titers were significantly higher among patients who had never smoked compared to patients who had ever smoked (P = 0.0049). Among nonsmokers, high anti-P gingivalis antibody levels were associated with a higher prevalence of erosive change (47.5% versus 33.3% with modified Sharp/van der Heijde score erosion subscale ≥1; P = 0.0135). In this large early RA cohort, we did not detect any association of anti-P gingivalis antibodies with RA or with ACPA status. These results suggest that the association of periodontitis and RA could be linked to bacterial species other than P gingivalis or to a mechanism other than citrullination. Nevertheless, we found higher anti-P gingivalis antibody titers in nonsmokers. In addition, in this population of nonsmokers, high anti-P gingivalis antibody titers were associated with more severe disease. We hypothesize that the role of tobacco in RA pathogenesis is so high that the effect of P gingivalis could be revealed only in a population not exposed to tobacco. © 2015, American College of Rheumatology.
Hitchon, Carol A; Alex, Philip; Erdile, Lawrence B; Frank, Mark B; Dozmorov, Igor; Tang, Yuhong; Wong, Keng; Centola, Michael; El-Gabalawy, Hani S
Early inflammatory arthritis is clinically heterogenous and biologically-based indicators are needed to distinguish severe from self-limited disease. Anti-cyclical citrullinated peptides (CCP) have been identified as potential prognostic markers in early arthritis cohorts. Since cytokine networks are known to play a critical role in the pathogenesis of rheumatoid arthritis (RA) and other forms of inflammatory arthritis, a panel of pro- and antiinflammatory cytokines was measured to identify biologically-based subsets of early arthritis, relating cytokine profiles to clinical measures and to the presence of RA-associated autoantibodies. Plasma concentrations of cytokines [interleukin 1beta (IL-1beta), IL-2, IL-4, IL-5, IL-6, IL-7, CXCL8 (IL-8), IL-10, IL-12p70, IL-13, IL-17, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon-g (IFN-g), CCL2 (monocyte chemoattractant protein-1, MCP-1), CCL4 (MIP-1beta), and tumor necrosis factor-a (TNF-a)] were measured in patients with early, untreated inflammatory arthritis [symptom duration < or = 12 months; > or = 1 swollen joint; RA, n = 41; undifferentiated arthritis (UA), n = 23]. Cytokine expression patterns were determined using cluster analysis. Both pro- and antiinflammatory cytokines were elevated in patients over controls (n = 21). RA clustered into subgroups based solely on cytokine profiles. The "mild" RA subgroup (n = 23) had higher CCL4 (MIP-1beta), CXCL8 (IL-8), IL-2, IL-12, IL-17, IL-5, and IL-10 levels, lower IL-6, IFN-g, GM-CSF, and IL-4 levels, less CCP positivity (52% vs 82%; p < 0.05), and lower CCP titers [71 (78) vs 153 (94); p < 0.01], but similar erythrocyte sedimentation rate, C-reactive protein, and joint counts compared to the "severe" RA groups. CCL4 (MIP-1beta), IL-13, IL-12, TNF-a, and IL-4 best distinguished the groups. Combining UA with RA samples preserved cytokine subgroups and strengthened the autoantibody associations. Fewer UA
Chiowchanwisawakit, Praveena; Wattanamongkolsil, Luksame; Srinonprasert, Varalak; Petcharat, Chonachan; Siriwanarangsun, Palanan; Katchamart, Wanruchada
To validate the Thai language version of the Psoriasis Epidemiology Screening Tool (PEST) and the Early Arthritis for Psoriatic Patients Questionnaire (EARP), as well as also to develop a new tool for screening psoriatic arthritis (PsA) among psoriasis (Ps) patients. This was a cross-sectional study. Ps patients visiting the psoriasis clinic at Siriraj Hospital were recruited. They completed the EARP and PEST. Full musculoskeletal history, examination, and radiography were evaluated. PsA was diagnosed by a rheumatologist's evaluation and fulfillment of the classification criteria for psoriatic arthritis. Receiver operator characteristic (ROC) curves, sensitivity, and specificity were used to evaluate the performances of the tools. The Siriraj Psoriatic Arthritis Screening Tool (SiPAT) contained questions most relevant to peripheral arthritis, axial inflammation, and enthesitis, selected from multivariate analysis. Of a total of 159 patients, the prevalence of PsA was 78.6 %. The ROC curve analyses of Thai EARP, PEST, and SiPAT were 0.90 (95 % CI 0.84, 0.96), 0.85 (0.78, 0.92), and 0.89 (0.83, 0.95), respectively. The sensitivities of SiPAT, Thai EARP, and PEST were 91.0, 83.0, and 72.0 %, respectively, while the specificities were 69.0, 79.3, and 89.7 %, respectively. All screening questionnaires showed good diagnostic performances. SiPAT could be considered as a screening tool with its desirable properties: higher sensitivity and taking less time. Thai PEST and EARP could possibly be sequentially administered for people with a positive test from SiPAT to reduce the number of false positives.
Rydholm, Maria; Book, Christina; Wikström, Ingegerd; Jacobsson, Lennart; Turesson, Carl
Objective measures of function are important in rheumatoid arthritis (RA). The objective of this study was to investigate grip strength in patients with early RA. An inception cohort of 225 patients with early RA was followed according to a structured protocol. Average and peak grip force values (Grippit; AB Detektor, Gothenburg, Sweden) of the dominant hand were evaluated and compared to the expected, based on age- and sex-specific reference values from the literature. Separate analyses were performed for those with limited self-reported disability (Health Assessment Questionnaire Disability Index (HAQ-DI) ≤ 0.5) and clinical remission (DAS28<2.6). The mean baseline average grip force was significantly lower than the corresponding expected values (105 N vs 266 N; p<0.001). Observed average and peak grip force values were significantly reduced compared to the expected in women as well as in men over time and at all time points. The average grip force improved significantly from inclusion to the 12 month visit [age-corrected mean change: 34 N; 95% confidence interval 26-43]. At 5 years, the average grip force was still lower than expected overall (mean 139 N vs 244 N; p<0.001), and also among those with HAQ-DI ≤ 0.5, and those in clinical remission. Grip strength improved in early RA, in particular during the first year. It was still significantly impaired 5 years after diagnosis, even among those with limited self-reported disability and those in clinical remission. This suggests that further efforts to improve hand function are important in early RA. This article is protected by copyright. All rights reserved. © 2017, American College of Rheumatology.
Narváez, José A; Narváez, Javier; De Lama, Eugenia; De Albert, Matías
Early diagnosis and treatment have been recognized as essential for improving clinical outcomes in patients with early rheumatoid arthritis. However, diagnosis is somewhat difficult in the early stages of the disease because the diagnostic criteria were developed from data obtained in patients with established rheumatoid arthritis and therefore are not readily applicable. Magnetic resonance (MR) imaging is increasingly being used in the assessment of rheumatoid arthritis due to its capacity to help identify the key pathologic features of this disease entity at presentation. MR imaging has demonstrated greater sensitivity for the detection of synovitis and erosions than either clinical examination or conventional radiography and can help establish an early diagnosis of rheumatoid arthritis. It also allows the detection of bone marrow edema, which is thought to be a precursor for the development of erosions in early rheumatoid arthritis as well as a marker of active inflammation. In addition, MR imaging can help differentiate rheumatoid arthritis from some clinical subsets of peripheral spondyloarthropathies by allowing identification of inflammation at the insertions of ligaments and tendons (enthesitis).
Diniz, Leonardo Rios; Balsamo, Sandor; Souza, Talita Yokoy de; Muniz, Luciana Feitosa; Martins, Wagner Rodrigues; Mota, Licia Maria Henrique da
To assess the prevalence of fatigue in a Brazilian population with early rheumatoid arthritis using multiple instruments, and the predictors of these instruments by differents independent variables. Cross-sectional study with direct interview and medical records review. Fatigue, dependent variable, was assessed using eight instruments: Profile of Mood States (POMS), Multidimensional Assessment of Fatigue scale (MAF), Fatigue Severity Scale (FSS), Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ), Numerical Rating Scales (BRAF-NRS), Short-form Survey 36 (SF-36), Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) and Visual Analogic Scale for Fatigue (VASf). sociodemographic, clinical and serological, were measured using medical records and direct interview. Disability and disease activity were assessed using the Health Assessment Questionnaire (HAQ) and disease activity assessed using the Disease Activity Score 28 joints (DAS28). The scores of scales demonstrated the level of fatigue and multiple linear regression method used in statistical analysis to demonstrate prediction models. A total of 80 patients was assessed, and 57 reported clinically relevant fatigue (VASf>2), representing 71.25% prevalence point (51 women [89.5%], mean age 48.35±15 years, and mean disease duration of 4.92±3.8 years). Eight predictive models showed statistical significance, one for each fatigue instrument. The highest coefficient of determination (R(2)) was 56% for SF-36 and the lowest (R(2)=21%) for FSS. The HAQ was the only independent variable to predict fatigue on all instruments. Clinically relevant fatigue is a highly prevalent symptom and is mostly predicted by disability and age in the population assessed. Copyright © 2017 Elsevier Editora Ltda. All rights reserved.
Huo, Yinghe; Vincken, Koen L; van der Heijde, Desiree; De Hair, Maria J H; Lafeber, Floris P; Viergever, Max A
The assessment of joint space width (JSW) on hand X-ray images of patients suffering from rheumatoid arthritis (RA) is a time-consuming task. Manual assessment is semiquantitative and is observer dependent which hinders an accurate evaluation of joint damage, particularly in the early stages. Automated analysis of the JSW is an important step forward since it is observer independent and might improve the assessment sensitivity in the early RA stage. This study proposes a fully automatic method for both joint location and margin detection in RA hand radiographs. The location detection procedure is based on image features of the joint region and is aided by geometric relationship of finger joints. More than 99% of joint locations are detected with an error smaller than 3 mm with respect to the manually indicated gold standard. The joint margins are detected by combining intensity values and spatially constrained intensity derivatives, refined by an active contour model. More than 96% of the joints are successfully delineated. The JSW is calculated over the middle 60% of a landmark-defined joint span. The overall JSW error compared with the ground truth is 6.8%. In conclusion, the proposed method is able to automatically locate the finger joints in RA hand radiographs, and to quantify the JSW of these joints.
Gibson, Kellie S; Woodburn, James; Porter, Duncan; Telfer, Scott
To investigate the mode-of-action and patient experience of functionally optimized foot orthoses in patients with early rheumatoid arthritis (RA). We conducted an investigation of 2 functionally optimized foot orthoses (selective laser sintering [SLS] and fused deposition modelling [FDM]) in 15 patients with RA of <2 years duration. The novel devices were optimized for 3 biomechanistic targets exploiting computer-aided design and additive manufacturing. A third standard device was used as the comparator (standard foot orthosis [SFO]). Foot and ankle biomechanical effects were compared. Adverse reactions, orthotic fit and comfort, and short-term symptom benefits were also monitored. Both FDM (P = 0.028) and SLS (P < 0.0001) orthoses significantly reduced peak rearfoot motion in comparison to shod. The average ankle internal moment was significantly decreased in the SFO (P = 0.010) and approached significance in the SLS (P = 0.052) orthosis. SFO, FDM, and SLS orthoses significantly increased the peak height of the medial foot arch between 3.6 to 4.4 mm (P < 0.001). Peak pressures in the medial (P = 0.018) and lateral forefoot (P = 0.022) regions of interest were significantly reduced for the SLS orthosis. SFO, FDM, and SLS orthoses significantly increased midfoot contact area (P < 0.001 for all conditions). In comparison to SFO, SLS and FDM orthoses provided equivalent or better patient experience. No adverse reactions were reported. Functional optimization is a feasible approach for orthoses prescription in early RA and has the potential to provide superior mode-of-action responses for biomechanical therapeutic targets compared to standard devices. Copyright © 2014 by the American College of Rheumatology.
van Schaardenburg, Dirkjan; Dijkmans, Ben A C
Several advances have been made in the understanding of the pathogenesis, as well as in the clinical evaluation and treatment, of early inflammatory arthritis. The presence of anti-citrullinated protein antibodies (ACPAs) has emerged as a major new biomarker for use in clinical practice. The presence of ACPAs can be used to divide patients with early arthritis into subsets that are phenotypically similar but have varying pathogenetic and prognostic features. Although the detection of ACPAs is a major development in the diagnosis and prognosis of rheumatoid arthritis (RA), prediction of the outcome of arthritis at the individual level can still be much improved. For patients diagnosed with RA, and who have active polyarthritis, treatment is not dependent on the assessment of prognostic factors, as these patients are best treated with combination therapy; over 40% of these patients achieve remission with such treatment. In patients who present with oligoarthritis, however, management should be based on the assessment of prognostic factors. The success of early treatment of inflammatory arthritis and the recognition of a measurable preclinical phase of RA offer hope that treating the disease before it becomes clinically active might be possible.
Maijer, Karen I; van der Leij, Christiaan; de Hair, Maria J H; Tas, Sander W; Maas, Mario; Gerlag, Daniëlle M; Tak, Paul P; Lavini, Cristina
Analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using pharmacokinetic modeling (PKM) provides quantitative measures that mirror microvessel integrity and can be used as an objective marker of the level of synovial inflammation. The aim of this study was to investigate the PKM parameters K(trans) , kep , and ve in a prospective cohort of disease-modifying antirheumatic drug (DMARD)-naive patients with early arthritis, and to validate the results by assessing their correlation with the number of synovial endothelial cells (ECs). Forty-seven patients with early arthritis (arthritis duration <1 year, DMARD naive; comprising 14 patients with rheumatoid arthritis, 22 with unclassified arthritis, 6 with spondyloarthritis [SpA], and 5 with other arthritides) were included. At baseline, DCE-MRI was performed on an inflamed knee joint of each patient. These images were used to calculate the K(trans) (volume transfer constant between the plasma and extracellular extravascular space [EES]), the kep (transfer constant between the EES and plasma), and the ve (fractional volume of the EES). Second, markers of disease activity were collected. Finally, vascularity was evaluated by immunohistochemical analysis of synovial tissue samples obtained from the inflamed knee joints, using antibodies to detect von Willebrand factor (vWF), a marker of ECs. The 3 PKM parameters differed significantly between diagnostic groups at baseline, with the highest K(trans) value being observed in patients with SpA (median 0.050/minute, interquartile range [IQR] 0.041- 0.069). Furthermore, the K(trans) , kep , and ve values correlated significantly with markers of disease activity. Finally, the PKM parameters K(trans) and kep , but not ve , correlated significantly with synovial expression of vWF (r = 0.647, P = 0.004 for K(trans) ; r = 0.614, P = 0.007 for kep ; r = 0.398, P = 0.102 for ve ). These results suggest that the K(trans) , kep , and ve can
Bilberg, A; Bremell, T; Balogh, I; Mannerkorpi, K
The aim of this study was to investigate work status and associated factors in patients with early rheumatoid arthritis (RA), with the emphasis on shoulder function, work-related mechanical exposure, and activity limitations related to the shoulder-arm-hand. Patients with early RA were provided with self-report questionnaires quantifying work-related mechanical exposure and activity limitations. Shoulder function (i.e. isometric muscle strength, shoulder-arm movement, and shoulder pain), hand-grip force, and number of tender and swollen joints were assessed. The study comprised 135 patients (103 women and 32 men), with a mean age of 48 (SD 9.6) years, a mean disease duration of 21 (SD 9.6) months, and a mean Disease Activity Score using 28 joint counts (DAS28) of 3.7 (SD 1.4). The majority (75.6%) were working full- or part-time. Work hours correlated with work-related mechanical exposure (rs = -0.34, p < 0.001) and with physical work load (rs = 0.26, p = 0.0036). Work hours also correlated with shoulder function, that is shoulder-arm movement (rs = 0.34, p < 0.0001), shoulder strength (rs = 0.25, p = 0.0032), and activity-induced shoulder pain (rs = -0.45, p < 0.0001). Significant correlations were found between work hours and hand-grip force (rs = 0.45, p < 0.0001), activity limitations related to the shoulder-arm-hand (using the Disabilities of the Arm, Shoulder and Hand Questionnaire, DASH) (rs = -0.61, p < 0.0001), and DAS28 (rs = -0.43, p < 0.0001). DASH was found to be the only significant (p < 0.001) variable to independently explain the ability of working full-time [odds ratio (OR) 0.40, 95% confidence interval (CI) 0.29-0.55 per 10 increments, area under the receiver operating characteristic (ROC) curve (AUC) 0.81, 95% CI 0.74-0.89]. Work status in early RA is associated with shoulder function and activity limitations related to the shoulder-arm-hand accentuated by work-related mechanical exposure.
Matthijssen, X M E; Markusse, I M; Stijnen, T; Riyazi, N; Han, K H; Bijkerk, C; Kerstens, P J S M; Lems, W F; Huizinga, T W J; Allaart, C F
Background Joint space narrowing (JSN) in rheumatoid arthritis (RA) may be a manifestation of (primary) osteoarthritis becoming more prominent with age. We investigated the severity and predictors of JSN progression among different age groups. Methods 10-year follow-up data of the BeSt study, a randomised controlled treat-to-target trial in early RA were used. Annual X-rays of hands and feet were scored using the Sharp/van der Heijde score (SHS). Subgroups were defined by age at baseline: ≥55, ≥40<55 and <40 years. JSN progression predictors were assessed by Poisson regression. Results Baseline JSN scores (median (IQR)) were higher in patients ≥55 (2.0 (0.0–6.0)) compared with the other age groups: 1.0 (0.0–3.0) ≥40<55 and 0.3 (0.0–3.0) <40, p<0.001. After 10 years, total JSN and SHS were similar in all age groups. In patients ≥55 the mean erythrocyte sedimentation rate (ESR) over time (relative risk 1.02 (95% CI 1.00 to 1.03)) and the combined presence of rheumatoid factor and anticitrullinated protein antibodies (RF+/ACPA+) (3.27 (1.25–8.53)) were significantly correlated with JSN progression. In patients <40 the baseline swollen joint count (SJC; 1.09 (1.01–1.18)) and ESR over time (1.04 (1.02–1.06)) were significantly associated. Conclusions At baseline, patients with RA ≥55 years had more JSN than younger patients but after 10 years JSN scores were similar between age groups. Independent risk factors for JSN progression were baseline SJC and ESR over time in patients <40, RF+/ACPA+ and ESR over time in patients ≥55 years. This suggests that mechanisms leading to JSN progression are related to (residual) rheumatoid inflammation and vary between age groups. These mechanisms remain to be elucidated. Trial registration numbers NTR262, NTR265. PMID:27843577
Matthijssen, X M E; Akdemir, G; Markusse, I M; Stijnen, T; Riyazi, N; Han, K H; Bijkerk, C; Kerstens, P J S M; Lems, W F; Huizinga, T W J; Allaart, C F
Joint space narrowing (JSN) in rheumatoid arthritis (RA) may be a manifestation of (primary) osteoarthritis becoming more prominent with age. We investigated the severity and predictors of JSN progression among different age groups. 10-year follow-up data of the BeSt study, a randomised controlled treat-to-target trial in early RA were used. Annual X-rays of hands and feet were scored using the Sharp/van der Heijde score (SHS). Subgroups were defined by age at baseline: ≥55, ≥40<55 and <40 years. JSN progression predictors were assessed by Poisson regression. Baseline JSN scores (median (IQR)) were higher in patients ≥55 (2.0 (0.0-6.0)) compared with the other age groups: 1.0 (0.0-3.0) ≥40<55 and 0.3 (0.0-3.0) <40, p<0.001. After 10 years, total JSN and SHS were similar in all age groups. In patients ≥55 the mean erythrocyte sedimentation rate (ESR) over time (relative risk 1.02 (95% CI 1.00 to 1.03)) and the combined presence of rheumatoid factor and anticitrullinated protein antibodies (RF+/ACPA+) (3.27 (1.25-8.53)) were significantly correlated with JSN progression. In patients <40 the baseline swollen joint count (SJC; 1.09 (1.01-1.18)) and ESR over time (1.04 (1.02-1.06)) were significantly associated. At baseline, patients with RA ≥55 years had more JSN than younger patients but after 10 years JSN scores were similar between age groups. Independent risk factors for JSN progression were baseline SJC and ESR over time in patients <40, RF+/ACPA+ and ESR over time in patients ≥55 years. This suggests that mechanisms leading to JSN progression are related to (residual) rheumatoid inflammation and vary between age groups. These mechanisms remain to be elucidated. NTR262, NTR265.
Mateo Soria, L; Miquel Nolla Solé, J; Rozadilla Sacanell, A; Valverde García, J; Roig Escofet, D
Eleven cases of infectious arthritis occurring in patients with rheumatoid arthritis are reported. Staphylococcus aureus was the causative organism in eight patients. Streptococcus anginosus and Streptococcus agalactiae in one patient each, and Mycobacterium tuberculosis in two patients. The mean duration of symptoms before diagnosis was 16 days in patients with pyogenic arthritis. The diagnosis of joint infection caused by Mycobacterium tuberculosis was especially delayed (57 days). Four patients died; they were found to have a longer time to diagnosis and two of them had multiple joint infection. Although Staphylococcus aureus is the microorganism most often affecting patients with rheumatoid arthritis, infection caused by Mycobacterium tuberculosis must also be considered in such patients. PMID:1575593
Barouta, Georgia; Katsiari, Christina G; Alexiou, Ioannis; Liaskos, Christos; Varna, Areti; Bogdanos, Dimitrios P; Germenis, Anastasios E; Sakkas, Lazaros I
This study aimed to assess the diagnostic and prognostic value of anti-mutated citrullinated vimentin (MCV) antibodies in very early rheumatoid arthritis (VERA) and in established rheumatoid arthritis (RA). Seventy-one patients with undifferentiated arthritis (UA) of <3 months duration, 141 with established RA, 53 with other rheumatic diseases, and 40 healthy individuals were included in the study. Anti-MCV, anti-cyclic citrullinated peptide (CCP) antibodies, and rheumatoid factor (RF) were determined and hand radiographs were recorded. Patients were assessed prospectively for 2 years, and hand radiographs were repeated. Diagnostic performance of anti-MCV was studied with receiver operating characteristic (ROC) curves and evaluation of sensitivity, specificity, and likelihood ratios. Forty-six percent of UA patients progressed to RA at 2 years. In VERA patients, sensitivity of anti-MCV was 52 %, compared to 44 % of anti-CCP and 37 % of RF, while specificity was 91 %, compared to 91 % of RF and 84 % of anti-CCP. Anti-MCV were detected in 25 % of VERA patients negative for both anti-CCP and RF. In established RA, anti-MCV did not sustain its diagnostic performance. By multivariable analysis, anti-MCV, but not anti-CCP or RF, showed significant correlation with radiographic progression in VERA patients. In established RA, anti-MCV, anti-CCP, and RF were associated with active disease (p ≤ 0.03) and joint damage (p ≤ 0.004). By multivariate analysis, the strongest factors for radiographic damage were disease duration (p = 0.000), HAQ score (p = 0.000), and RF (p = 0.002). In conclusion, in patients with very early UA, anti-MCV predict both progression to RA and radiological damage, and therefore, anti-MCV antibody testing may be useful in every day practice.
Gwinnutt, James M; Symmons, Deborah P M; MacGregor, Alexander J; Chipping, Jacqueline R; Marshall, Tarnya; Lunt, Mark; Verstappen, Suzanne M M
To describe the outcome in patients with rheumatoid arthritis (RA) over 20 years from symptom onset, and to assess the association between early treatment (with disease-modifying antirheumatic drugs/steroids) and mortality and disability during follow-up. Patients recruited to the Norfolk Arthritis Register (NOAR) between 1990 and 1994 who met the 2010 American College of Rheumatology/European League Against Rheumatism RA criteria at baseline were included in this analysis. Demographic and clinical variables were collected at baseline and at years 1-3, 5, 7, 10, 15, and 20. Disease activity (swollen joint count [SJC]/tender joint count [TJC]), disability (Health Assessment Questionnaire disability index [HAQ DI]), and mortality over 20 years were determined. Associations between treatment group (early treatment [ET], treatment ≤6 months after symptom onset; late treatment [LT], treatment >6 months after symptom onset; never treatment [NT], no treatment) and mortality and disability were assessed using weighted pooled logistic regression and weighted multilevel mixed-effects linear regression, respectively. Inverse weights were used to account for confounding by indication and censoring. This study included 602 patients with RA (median age 56 years [interquartile range 44-68 years]; 65.9% women). The median SJCs and TJCs were low during the follow-up period (1-3 swollen joints and 3-6 tender joints). The median HAQ DI score increased after year 1 but remained at low/moderate levels (median 1.25 after year 10). The risk of mortality was reduced in the ET and LT groups compared with that in the NT group. The ET group and the NT group had comparable HAQ DI scores during the follow-up period (β = 0.03, 95% confidence interval [95% CI] -0.06, 0.12), while the HAQ DI score was increased in the LT group (for LT versus NT, β = 0.10 [95% CI 0.02, 0.17]). The results of this study indicate the importance of early treatment with regard to the long-term outcomes in
Nam, Jackie L
Early effective treatment has led to major improvements in patients with rheumatoid arthritis. This review aims to address the treatment of early rheumatoid arthritis, in particular the different therapeutic strategies evaluated in clinical trials to achieve optimal disease control. The use of biological disease-modifying antirheumatic drugs (bDMARDs) has significantly improved patient outcomes. Overall, studies using bDMARD induction have shown early clinical improvements, with high proportions achieving remission with minimal radiographic progression. As these drugs are still relatively costly, conventional synthetic DMARDs, as monotherapy or in combination, remain the mainstay of treatment initiation. Good, albeit somewhat slower, responses can be achieved with these drugs. Strategies incorporating glucocorticoids and a treat-to-target approach (i.e. regular monitoring of disease activity and early treatment escalation with a conventional synthetic or b-DMARD, if needed) have shown additional benefit. In patients achieving low disease activity or remission, bDMARD dose reduction and withdrawal, and even drug-free remission have been possible in some. In patients with early rheumatoid arthritis, conventional synthetic DMARDs and glucocorticoids used within a treat-to-target setting, and the addition of a bDMARD if required, outcomes have improved significantly. A proportion of patients are able to deescalate treatment after bDMARD therapy, with a significant minority achieving drug-free remission.
Gottenberg, Jacques-Eric; Miceli-Richard, Corinne; Ducot, Béatrice; Goupille, Philippe; Combe, Bernard; Mariette, Xavier
Little is known about systemic B-cell activation in early rheumatoid arthritis (RA). We therefore evaluated the serum levels of markers of B-cell activation in patients included in the ESPOIR early arthritis cohort. In the ESPOIR early arthritis cohort (at least 2 swollen joints for more than 6 weeks but less than 6 months), 710 patients were assessed at 1 year and either met the 1987 American College of Rheumatology criteria for RA (n = 578) or had undifferentiated arthritis (n = 132). Baseline serum samples of patients naïve to corticosteroid and disease-modifying antirheumatic drug treatment were assessed for beta2-microglobulin, IgG, IgA, IgM, immunoglobulin free light chains of immunoglobulins, and B-cell activating factor of the tumor necrosis factor family (BAFF). The BAFF gene 871T>C polymorphism was genotyped in all patients. All markers of B-cell activation except BAFF and IgM were significantly higher in patients with early RA than those with undifferentiated arthritis. Anti-cyclic citrullinated peptide (anti-CCP) and beta2-microglobulin were associated with a diagnosis of early RA in the multivariate analysis. Markers of B-cell activation, except BAFF, were associated with disease activity, rheumatoid factor and anti-CCP secretion. The BAFF gene polymorphism was not associated with early RA. Markers of B-cell activation are elevated in patients with early RA, compared with undifferentiated arthritis, independently of any systemic increase in BAFF secretion, and correlate with disease activity. This study sheds new light on the early pathogenic role of B-lymphocytes in RA and suggests that targeting them might be a useful therapeutic strategy in early RA.
Clements, J; Dinneen, A; Heilpern, G
Septic arthritis is an uncommon condition with an incidence of 2-3/100,000. It is clinically notable, however, as it is a rapidly destructive joint disease with significant associated morbidity and mortality. Polyarticular septic arthritis has an estimated incidence of 15% of all cases of infectious arthritis. We report a case of polyarticular septic arthritis with involvement of bilateral shoulders and wrist to highlight the importance of early diagnosis and treatment as well as the high mortality rates associated with this condition. Bilateral septic shoulder arthritis poses a challenge to treat, and its significance should not be underestimated as even with early surgical intervention and aggressive antibiotic and fluid resuscitation death is a sad but perhaps not uncommon outcome. It is therefore imperative that the diagnosis of polyarticular septic arthritis is kept prominent in the physician's mind when confronted with a patient with symptomatic polyarthralgia.
Pérez-Barbosa, L; Esquivel-Valerio, J A; Arana-Guajardo, A C; Vega-Morales, D; Riega-Torres, J; Garza-Elizondo, M A
The incidence of tuberculosis (TB) in rheumatoid arthritis (RA) patients is up to four times higher when compared to the general population, but their risk increases with the use of TNF-a drugs. Appropriate screening of latent tuberculosis infection (LTBI) and proper management of such cases substantially reduce the incidence of active TB. Tuberculin skin test (TST) is a widely used method for the detection of LTBI. The time of diagnosis of RA as well as the age of the patient might modify the TST performance. We did an observational, comparative study of RA patients with early and established disease, with the objective to know the prevalence of LTBI using the TST and booster test; an induration ≥5 mm was considered reactive. We evaluated 143 patients (83 [58 %] early RA patients). We found 31.3 and 21.7 % TST positivity in early and established RA patients, respectively. With the use of booster test, the positivity increased to 46.5 and 28.8 %, respectively (p = 0.048, OR 1.33, 95 % CI 1.01-1.75). In conclusion, we found that TST and booster test increased LTBI detection in early RA patients, which may suggest that time of RA diagnosis might affect cellular immunity and therefore the TST response.
McQueen, Fiona M
Imaging in early rheumatoid arthritis (RA) has undergone extraordinary change in recent years and new techniques are now available to help the clinician diagnose and manage patients much more effectively than previously. While established modalities such as plain radiography (X-Ray) remain important, especially for detection of erosions and determining the progression of joint damage, there are many instances where ultrasound (US), magnetic resonance imaging (MRI) and computed tomography (CT) scanning provide added information. MRI and US are now used regularly by clinicians to help diagnose RA in the pre-radiographic stage as they offer improved visualisation of joint erosions. They also have the potential to provide prognostic information as MRI bone oedema/osteitis is linked to the later development of erosions and power Doppler ultrasound (PDUS) joint positivity is also a predictor of joint damage. Nuclear imaging techniques such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) are also highly sensitive for detecting joint change in early RA and pre-RA but not yet used clinically mainly because of accessibility and radiation exposure. MRI, US, scintigraphy, SPECT and PET have all been shown to detect sub-clinical joint inflammation in patients in clinical remission, a state that is now the goal of most treat-to-target management strategies. Thus, imaging may be used to direct therapeutic decision making and MRI is also now being used in clinical trials to determine the impact of disease-suppressing therapy on the course of synovitis and osteitis. As is the case for all tests, it would be unwise to rely completely on any one imaging result, as false positives and negatives can occur for all modalities. Thus, the clinician needs to choose the most relevant and reliable imaging test, while also striving to minimise patient discomfort, radiation burden and economic impact.
Kudo-Tanaka, Eriko; Shimizu, Takashi; Nii, Takuro; Teshigawara, Satoru; Yoshimura, Maiko; Watanabe, Akane; Tsuji, Soichiro; Tsuboi, Hideki; Hirao, Makoto; Yura, Akiko; Harada, Yoshinori; Sueishi, Makoto; Suenaga, Yasuo; Chiba, Noriyuki; Tonai, Takeharu; Saisho, Koichiro; Ogata, Atsushi; Matsushita, Masato; Hashimoto, Jun; Ohshima, Shiro; Tohma, Shigeto; Saeki, Yukihiko
To examine whether or not earlier therapeutic intervention with methotrexate (MTX) prevents the development of rheumatoid arthritis (RA) in patients with recent-onset undifferentiated arthritis (UA) showing high anti-citrullinated peptide antibody (ACPA) titers. The patients were divided into two groups, one was treated with MTX (MTX+ group, n = 29), and the other was treated without MTX (MTX- group, n = 19), and other disease-modifying anti-rheumatic drugs were not permitted in the two groups before the primary endpoint was met. The primary endpoint is the occurrence of definite RA, and it was compared in the two groups after 1 year. The percentage of patients who developed definite RA in the MTX+ group (17.2%) was significantly lower than that in the MTX- group (78.9%) (log-rank test, P < 0.001, n = 48); adjusted hazards ratio: 0.028 [95% confidence interval (CI): 0.003-0.250, P = 0.001, n = 39]. Treatment effectiveness was not decreased by major risk factors of RA onset such as smoking habits and human leukocyte antigen-DRB1 shared epitope (SE) (smoking habit, odds ratio [OR]: 0.041 [95% CI: 0.007-0.246] P < 0.001; SE, OR: 0.022 [95% CI: 0.002-0.204] P < 0.001). The safety issues were comparable between the two groups. This suggests that early therapeutic intervention with MTX could safely prevent the development of RA in patients with recent-onset UA showing high ACPA titers.
Curtis, J R; Yang, S; Chen, L; Pope, J E; Keystone, E C; Haraoui, B; Boire, G; Thorne, J C; Tin, D; Hitchon, C A; Bingham, C O; Bykerk, V P
Simplified measures to quantify rheumatoid arthritis (RA) disease activity are increasingly used. The minimum clinically important differences (MCID) for some measures, such as the Clinical Disease Activity Index (CDAI), have not been well-defined in real-world clinic settings, especially for early RA patients with low/moderate disease activity. Data from Canadian Early Arthritis Cohort patients were used to examine absolute change in CDAI in the first year after enrollment, stratified by disease activity. MCID cut points were derived to optimize the sum of sensitivity and specificity versus the gold standard of patient self-reported improvement or worsening. Sensitivity, specificity, positive predictive values, and negative predictive values were calculated against patient self-reported improvement (gold standard) and for change in pain, Health Assessment Questionnaire (HAQ), and Disease Activity Score in 28 joints (DAS28) improvement. Discrimination was examined using the area under receiver operator curves. Similar methods were used to evaluate MCIDs for worsening for patients who achieved low disease activity. A total of 578 patients (mean ± SD age 54.1 ± 15.3 years, 75% women, median [interquartile range] disease duration 5.3 [3.3, 8.0] months) contributed 1,169 visit pairs to the improvement analysis. The MCID cut points for improvement were 12 (patients starting in high disease activity: CDAI >22), 6 (moderate: CDAI 10-22), and 1 (low disease activity: CDAI <10). Performance characteristics were acceptable using these cut points for pain, HAQ, and DAS28. The MCID for CDAI worsening among patients who achieved low disease activity was 2 units. These minimum important absolute differences in CDAI can be used to evaluate improvement and worsening and increase the utility of CDAI in clinical practice. © 2015, American College of Rheumatology.
Peterfy, Charles; Burmester, Gerd R; Bykerk, Vivian P; Combe, Bernard G; DiCarlo, Julie C; Furst, Daniel E; Huizinga, Tom W J; Wong, Dennis A; Conaghan, Philip G; Emery, Paul
Objectives To assess structural damage progression with subcutaneous abatacept (ABA) in the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) trial following abrupt withdrawal of all rheumatoid arthritis (RA) medication in patients achieving Disease Activity Score (DAS)-defined remission or low disease activity. Methods Patients with early, active RA were randomised to ABA plus methotrexate (ABA/MTX) 125 mg/week, ABA 125 mg/week or MTX for 12 months. All RA treatments were withdrawn after 12 months in patients with DAS28 (C reactive protein (CRP)) <3.2. Adjusted mean changes from baseline in MRI-based synovitis, osteitis and erosion were calculated for the intention-to-treat population. Results 351 patients were randomised and treated: ABA/MTX (n=119), ABA (n=116) or MTX (n=116). Synovitis and osteitis improved, and progression of erosion was statistically less with ABA/MTX versus MTX at month 12 (−2.35 vs −0.68, −2.58 vs −0.68, 0.19 vs 1.53, respectively; p<0.01 for each) and month 18 (−1.34 vs −0.49 −2.03 vs 0.34, 0.13 vs 2.0, respectively; p<0.01 for erosion); ABA benefits were numerically intermediate to those for ABA/MTX and MTX. Conclusions Structural benefits with ABA/MTX or ABA may be maintained 6 months after withdrawal of all treatments in patients who have achieved remission or low disease activity. Trial registration number NCT01142726; Results. PMID:26865601
Lourdudoss, Cecilia; Di Giuseppe, Daniela; Wolk, Alicja; Westerlind, Helga; Klareskog, Lars; Alfredsson, Lars; van Vollenhoven, Ronald F; Lampa, Jon
Objective To investigate potential associations between dietary intake of polyunsaturated fatty acids (PUFA) and pain patterns in early rheumatoid arthritis (RA) patients after three months of methotrexate (MTX) treatment. Methods We included 591 early RA patients with MTX monotherapy from a population based prospective case-control study, the Epidemiological Investigation of Rheumatoid Arthritis (EIRA). Dietary data on PUFA (food frequency questionnaires) were linked with data on unacceptable pain (visual analogue scale (VAS) >40mm), non-inflammatory/refractory pain (VAS >40mm and C-reactive protein (CRP) <10mg/L) and inflammatory pain (VAS >40mm and CRP >10mg/L) after three months. Statistical analysis included logistic regression. Results After three months of MTX treatment, 125 patients (21.2%) had unacceptable pain, of which 92 patients had refractory pain and 33 patients had inflammatory pain. Omega-3 fatty acid (FA) intake was inversely associated with unacceptable pain and refractory pain (OR=0.57 [95% CI 0.35-0.95] and OR=0.47 [95% CI 0.26-0.84], respectively). Omega-6 to -3 FA ratio, but not omega-6 FA alone, was directly associated with unacceptable pain and refractory pain (OR=1.70 [95% CI 1.03-2.82] and OR=2.33 [95% CI 1.28-4.24], respectively). Furthermore, PUFA was not associated with neither inflammatory pain nor CRP and erythrocyte sedimentation rate at follow-up. Omega-3 FA supplementation was not associated with any pain patterns. Conclusion Omega-3 FA was inversely associated with, and omega-6 to -3 FA ratio was directly associated with unacceptable and refractory pain, but not with inflammatory pain or systemic inflammation. The inverse association between omega-3 FA and refractory pain may have a role in pain suppression in RA. This article is protected by copyright. All rights reserved.
Di Spigna, G; Del Puente, A; Covelli, B; Abete, E; Varriale, E; Salzano, S; Postiglione, L
Rheumatoid Arthritis (RA) is an autoimmune inflammatory disease that leads to local and systemic arthritis and bone loss. Exploring genetic markers of candidate genes in osteoporosis and inflammatory cytokine genes could be a useful tool for the early identification of bone loss and fracture risk in RA patients. The target of this study is the evaluation and correlation between of Single Nucleotide Polymorphisms (SNPs) of Vitamin D Receptor (VDR) and possible effects on bone loss in RA. 40 Caucasian patients with RA (26 of them with a severe bone loss) and 40 healthy donors as control samples were genotyped for the VDR SNPs (called BsmI, ApaI, TaqI and FokI). The detection method is based on Restriction Fragment Length Polymorphism (RFLP). Genotyping profile shown no difference between RA patients and controls. Only VDR-TaqI genotype (TT vs. tt) seem to influence the bone density in females, but not in males. The mean differences of Bone Mass Density (BMD) at the lumbar spine in RA women with the tt allele were 4.7% compared to 0.1% in women with the TT allele (p < 0.05). The results of these studies support an association between specific VDR alleles and bone loss in RA. The TaqI t and BsmI B alleles were associated with an accelerated bone loss in RA, but not with a focal bone loss. These effects of VDR genotypes and vitamin D supplementation are not unexpected, given that the central pathological feature in RA is bone and joint destruction. The VDR SNPs genotyping should be a useful tool to screen early women RA patients with the bone loss.
Mueller, R B; Schiff, M; Kaegi, T; Finckh, A; Haile, S R; Schulze-Koops, H; von Kempis, J
New American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for the classification of rheumatoid arthritis (RA) have recently been proposed. The aim of this cohort study was to examine whether fulfilling these 2010 ACR/EULAR criteria at the first visit has an impact on the clinical course and on the radiographic progression of the disease. For this observational cohort study, we included patients from the Swiss RA registry SCQM with early RA or undifferentiated arthritis (UA, disease duration ≤1 year), as defined by the treating rheumatologist, who had not received any previous disease modifying anti-rheumatic drugs (DMARDs). Patients were categorized into two groups depending on whether or not they fulfilled the 2010 ACR/EULAR criteria (≥6 points vs <6 points) at the first visit. The primary outcome measures were the evolution of the DAS 28 and of radiographic erosions as measured by the Ratingen score over time. Of the 592 patients fulfilling the inclusion criteria, 352 satisfied the 2010 ACR/EULAR criteria at baseline, whereas 240 were not classifiable as definite RA. The ACR/EULAR criteria scores correlated with disease activity at disease onset (R (2) = 0.31). DMARD treatment was subsequently initiated in all patients, mostly with methotrexate (MTX). There were no significant differences in the therapeutic strategies between patients fulfilling or not fulfilling the classification criteria. Six months after inclusion, patients fulfilling the ACR/EULAR criteria developed a 39.1 % reduction of DAS 28 scores, as compared to a 33.6 % reduction in patients not fulfilling the ACR/EULAR criteria (p = 0.0002), independently of their respective treatment strategy. Importantly, the DAS 28 scores were higher in those patients fulfilling the ACR/EULAR criteria (ACR/EULAR positive patients) throughout the observation, as compared to patients not fulfilling those (ACR/EULAR negative patients). Average radiographic progression
Akdemir, Gülşah; Verheul, Marije K; Heimans, Lotte; Wevers-de Boer, Kirsten V C; Goekoop-Ruiterman, Yvonne P M; van Oosterhout, Maikel; Harbers, Joop B; Bijkerk, Casper; Steup-Beekman, Gerda M; Lard, Leroy R; Huizinga, Tom W J; Trouw, Leendert A; Allaart, Cornelia F
Objectives To identify predictive factors of radiological progression in early arthritis patients treated by remission-steered treatment. Methods In the IMPROVED study, 610 patients with early rheumatoid arthritis (RA) or undifferentiated arthritis (UA) were treated with methotrexate (MTX) and a tapered high dose of prednisone. Patients in early remission (disease activity score (DAS) <1.6 after 4 months) tapered prednisone to zero. Patients not in early remission were randomised to arm 1: MTX plus hydroxychloroquine, sulfasalazine and prednisone, or to arm 2: MTX plus adalimumab. Predictors of radiological progression (≥0.5 Sharp/van der Heijde score; SHS) after 2 years were assessed using logistic regression analysis. Results Median (IQR) SHS progression in 488 patients was 0 (0–0) point, without differences between RA or UA patients or between treatment arms. In only 50/488 patients, the SHS progression was ≥0.5: 33 (66%) were in the early DAS remission group, 9 (18%) in arm 1, 5 (10%) in arm 2, 3 (6%) in the outside of protocol group. Age (OR (95% CI): 1.03 (1.00 to 1.06)) and the combined presence of anticarbamylated protein antibodies (anti-CarP) and anticitrullinated protein antibodies (ACPA) (2.54 (1.16 to 5.58)) were independent predictors for SHS progression. Symptom duration <12 weeks showed a trend. Conclusions After 2 years of remission steered treatment in early arthritis patients, there was limited SHS progression in only a small group of patients. Numerically, patients who had achieved early DAS remission had more SHS progression than other patients. Positivity for both anti-CarP and ACPA and age were independently associated with SHS progression. Trial registration numbers ISRCTN Register number 11916566 and EudraCT number 2006 06186-16. PMID:26925251
Dimic, Aleksandar; Milenkovic, Sasa; Krtinic, Dane; Aleksic, Ivana
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation and destruction of joint cartilage and bone. Different cytokines play important role in the processes that cause articular destruction and extra-articular manifestations in RA. The contribution of cytokines representing the Th1 (INF-γ), Th2 (IL-4) and IL-17A to the pathogenesis of early RA and bone mineral density (BMD) loss in still poorly understood. Serum samples of 38 early RA patients were evaluated for erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibodies (anti-CCP) and for the tested cytokines (IL-17A, IL-4 and INF-γ). BMD was evaluated by dualenergy X-ray absorptiometry (DXA). Disease activity score (DAS28) calculation was assessed for all patients. Control serum samples were obtained from 34 healthy volunteers. The levels of tested cytokines were significantly higher (IL-17A, p<0.001; INF-γ, P<0.001; IL-4, P<0.01) in patients with early RA, compared to the healthy controls. In early RA patients, strong correlation of serum IL-17A was found with DAS28, ESR and CRP. Also, a significant negative correlation was found between serum INF-γ levels and the DAS28 score. Significantly positive correlation of BMD values and CRP, DAS28 IL-17A were also demonstrated. DXA analysis revealed that the most common site for osteoporosis was the lumbar spine followed by the femoral neck. BMD values significantly correlated with CRP, DAS28 score and IL-17A serum levels. The mean serum IL-17A levels, in patients with early RA, corresponded with disease activity, severity and BMD loss, indicating the potential usefulness of serum IL-17A in defining the disease activity and bone remodeling. PMID:28352685
Combe, Bernard; Niu, Jingbo; Rincheval, Nathalie; Gaujoux-Viala, Cécile; Felson, David T.
Objective. To evaluate whether patients with RA who belong to the spectrum of fibromyalgic RA (FRA) have an impaired response to treatment measured by traditional activity scores. Methods. Patients from the ESPOIR cohort were analysed. This prospective cohort included 813 patients with early arthritis not initially receiving DMARDs. Among the 697 patients who met RA classification criteria, we studied two groups, one with and the other without FRA. The following endpoints were compared at 6, 12 and 18 months using a mixed linear regression model: 28-joint DAS (DAS28), Simple Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI) and HAQ. In addition, attainment of low disease activity (LDA; DAS28 <3.2) and remission (DAS28 <2.6, SDAI <3.3, CDAI <2.8) at these time points was analysed. Results. Patients with FRA (n = 120) had higher DAS28, SDAI, CDAI and HAQ scores than patients with RA and no fibromyalgic characteristics (n = 548). DAS28 and other DASs started out higher in subjects with FRA, and while they improved to a similar extent to in the isolated RA group, they remained consistently higher among FRA patients. Achievement of LDA and remission was significantly less likely in subjects with FRA. Conclusion. Patients with FRA and RA will have a similar response to treatment according to the decrease in indexes of disease activity, but may miss the target of remission or LDA. PMID:26175470
Abdulqader, Yasir; Al-Ani, Muhsen; Parperis, Konstantinos
Rheumatoid vasculitis is a rare and late complication of rheumatoid arthritis and may affect small-to-medium-sized vessels. Here, we report a case of a 49-year-old man who presented with amaurosis fugax in the left eye, symmetric polyarthritis, Raynaud's symptoms and paraesthesia in both lower extremities. The patient subsequently experienced right foot drop, nail fold infracts and gangrene of his right second toe. He was found to have a high titre of rheumatoid factor and treatment with rituximab and high dose of corticosteroids led to significant improvement of his symptoms. This is rare case describing the early onset of rheumatoid vasculitis in a patient with rheumatoid arthritis. 2016 BMJ Publishing Group Ltd.
Boers, M; Kostense, P J; Verhoeven, A C; van der Linden, S
OBJECTIVE; Several factors predict joint damage in early rheumatoid arthritis (RA). In the context of a trial in early RA, we studied the relationship between clinical signs in individual joints and their propensity to develop progressive damage. The COBRA (Combinatietherapie Bij Reumatoide Artritis) multicenter trial compared the efficacy of prednisolone, methotrexate, and sulfasalazine against sulfasalazine alone in 155 patients with early RA. Two blinded observers interpreted radiographs in sequence (using the Sharp/Van der Heijde scoring system); in each center, one blinded observer performed clinical assessments every 3 months. The current analysis is based on clinical and radiologic data of the individual metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of 135 patients. Conditional stepwise logistic regression analyzed the relationship between damage (progression) and clinical signs at baseline and followup for each of these joints individually in each patient. Combination therapy strongly retarded the progression of damage. Progression was stronger in patients with rheumatoid factor, HLA-DR4, and high levels of disease activity at baseline. At baseline, 6% of the MCP and PIP joints showed damage; after 1 year, disease had progressed in 10% of these joints. Baseline damage, swelling, or pain in a joint independently and strongly predicted the progression of damage in that joint (P < 0.001). Each additional point in the swelling score (range 0-2) tripled the risk for subsequent progression. Each additional point on the Sharp scale (range 0-8 per joint) and each additional point on the pain scale (range 0-3) doubled the risk. The mean pain and swelling scores over the year were even stronger predictors of damage. Local expression of early RA disease activity, both at baseline and at 1-year followup, is strongly related to progression of damage in the individual joint.
Wolff, Björn; Berger, Timo; Frese, Cornelia; Max, Regina; Blank, Norbert; Lorenz, Hanns-Martin; Wolff, Diana
Patients with RA suffer from a higher risk of periodontal attachment loss and increased oral inflammation. We hypothesize that there are pathogenetic and immunological interactions between these diseases that go beyond impaired manual dexterity accompanying advanced RA. The primary objective of the present study was to determine whether a loss of alveolar bone can be detected in RA patients during the early course of the disease. In this cross-sectional, epidemiological case-control study, 22 patients with early RA (ERA) were compared with 22 matched healthy controls. Oral and periodontal status, clinical activity, and socio-demographic parameters were determined. Oral microbiota were analysed using real-time quantitative PCR specific for leading oral pathogens. More advanced forms of periodontitis were found in ERA patients compared with controls. ERA patients had a greater number of missing teeth [ERA 5.7 (s.d. 5.0), controls 1.9 (s.d. 1.0), P = 0.002], deeper periodontal pockets [clinical attachment level: ERA 3.4 (s.d. 0.5 mm), controls 2.7 (s.d. 0.3 mm), P < 0.000], and greater bleeding on probing [ERA 18.6% (s.d. 9.0%), controls 10.5% (s.d. 5.1%), P = 0.001] despite comparable oral hygiene. Tannerella forsythia (6.77-fold, P = 0.033) subgingivally and Streptococcus anginosus (3.56-fold, P = 0.028) supragingivally were the characteristic pathogens in ERA. Increased loss of periodontal attachment and alveolar bone can be detected in patients with ERA, therefore we propose that the consulting rheumatologists inform the patients that they have a higher risk of periodontal disease. It would be beneficial if these patients were referred directly for intensive dental care.
Westhovens, R; Robles, M; Ximenes, A C; Nayiager, S; Wollenhaupt, J; Durez, P; Gomez-Reino, J; Grassi, W; Haraoui, B; Shergy, W; Park, S-H; Genant, H; Peterfy, C; Becker, J-C; Covucci, A; Helfrick, R; Bathon, J
Objectives: To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors. Methods: In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (∼10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score; TS) at year 1. Safety was monitored throughout. Results: At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5% and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At year 1, a significantly greater proportion of abatacept plus methotrexate-treated patients achieved remission (41.4% vs 23.3%; p<0.001) and there was significantly less radiographic progression (mean change in TS 0.63 vs 1.06; p = 0.040) versus methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (7.8% vs 7.9%), serious infections (2.0% vs 2.0%), autoimmune disorders (2.3% vs 2.0%) and malignancies (0.4% vs 0%) was comparable for abatacept plus methotrexate versus methotrexate alone. Conclusions: In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile. PMID:19124524
Lindqvist, E; Saxne, T; Geborek, P; Eberhardt, K
To investigate outcome as measured by health status, disease process, and damage in an unselected group of patients with early rheumatoid arthritis (RA) monitored prospectively for 10 years and to search for prognostic factors. 183 patients with RA with disease duration <2 years were assessed annually at a team care unit. Health status was measured by the Health Assessment Questionnaire (HAQ) and functional class. Disease process was assessed by clinical and laboratory measures of disease activity and evaluation of disease course. Damage was quantified as occurrence of major extra-articular manifestations and need for large joint replacements. Possible predictive factors were evaluated by logistic regression analyses. 168/183 patients completed the entire follow up period. Of all 183 patients, 137 (75%) had been treated with disease modifying antirheumatic drugs and 84 (46%) with low dose oral glucocorticoids. After 10 years 158 patients (94%) managed daily life activities independently (functional class I-II). As measured by the HAQ 20% had almost no disability, 28% were mildly disabled, and 10% were seriously disabled. Median HAQ score had increased from 0.8 to 1.1 (p<0.001). Disease activity was significantly reduced. 133 patients (79%) had a relapsing remitting disease course and 30 patients (18%) were in remission as defined by the American College of Rheumatology criteria. Thirty patients (17%) had undergone large joint replacements. Fifteen patients (8%) had developed major extra-articular complications. The HAQ score during the first three months predicted disability at 10 years with an odds ratio of 13.4. Prospective studies such as this give important knowledge of the variable long term prognosis of RA and provide necessary background information for clinical trials of new treatment modalities.
Filer, Andrew; de Pablo, Paola; Allen, Gina; Nightingale, Peter; Jordan, Alison; Jobanputra, Paresh; Bowman, Simon; Buckley, Christopher D; Raza, Karim
Objectives Early therapy improves outcomes in rheumatoid arthritis (RA). It is therefore important to improve predictive algorithms for RA in early disease. This study evaluated musculoskeletal ultrasound, a sensitive tool for the detection of synovitis and erosions, as a predictor of outcome in very early synovitis. Methods 58 patients with clinically apparent synovitis of at least one joint and symptom duration of ≤3 months underwent clinical, laboratory, radiographic and 38 joint ultrasound assessments and were followed prospectively for 18 months, determining outcome by 1987 American College of Rheumatology (ACR) and 2010 ACR/European League Against Rheumatism criteria. Sensitivity and specificity for 1987 RA criteria were determined for ultrasound variables and logistic regression models were then fitted to evaluate predictive ability over and above the Leiden rule. Results 16 patients resolved, 13 developed non-RA persistent disease and 29 developed RA by 1987 criteria. Ultrasound demonstrated subclinical wrist, elbow, knee, ankle and metatarsophalangeal joint involvement in patients developing RA. Large joint and proximal interphalangeal joint ultrasound variables had poor predictive ability, whereas ultrasound erosions lacked specificity. Regression analysis demonstrated that greyscale wrist and metacarpophalangeal joint involvement, and power Doppler involvement of metatarsophalangeal joints provided independently predictive data. Global ultrasound counts were inferior to minimal power Doppler counts, which significantly improved area under the curve values from 0.905 to 0.962 combined with the Leiden rule. Conclusion In a longitudinal study, extended ultrasound joint evaluation significantly increased detection of joint involvement in all regions and outcome groups. Greyscale and power Doppler scanning of metacarpophalangeal joints, wrists and metatarsophalangeal joints provides the optimum minimal ultrasound data to improve on clinical predictive
Introduction Autoantibodies against citrullinated peptides/proteins (ACPA) are found in approximately 75% of the sera of patients with rheumatoid arthritis (RA). The RA-specific ACPA are frequently present prior to disease onset and their presence associates with a more erosive disease course. ACPA can therefore be used to aid the diagnosis and prognosis of RA. Recently, it became clear that ACPA are very heterogeneous, both in an individual patient and among different patients. The aim of this study was to investigate whether clinically meaningful ACPA profiles exist in early RA patients. Methods Twenty citrullinated peptides and the corresponding non-citrullinated control peptides were immobilized on microarray sensor chips. Sera from 374 early arthritis patients were analyzed by surface plasmon resonance imaging (iSPR) of biomolecular interactions on the sensor chip. Results Cluster analysis of the reactivities with the citrullinated peptides, after subtraction of the reactivities with the corresponding control peptides confirmed the heterogeneity of the ACPA response in RA and revealed 12 distinct ACPA profiles. The association of the 5 most frequent profiles with clinical features at diagnosis and during the disease course was examined, showing no statistically significant associations. Conclusions Compared to the detection of ACPA in RA sera by CCP-based assays, ACPA profiling in early arthritis patients did not reveal associations with disease activity and progression scores. PMID:24286543
Robles-Perez, Alejandro; Luburich, Patricio; Rodriguez-Sanchon, Benigno; Dorca, Jordi; Nolla, Joan Miquel; Molina-Molina, Maria; Narvaez-Garcia, Javier
Early detection and treatment of lung disease in patients with rheumatoid arthritis (RA) may ameliorate disease progression. The objectives of this study were to investigate the frequency of asymptomatic lung abnormalities in early RA patients and the potential association of positive RA blood reactive biomolecules with lung involvement. A prospective observational study was performed in a cohort of patients with early RA (joint symptoms < 2 years) without respiratory symptoms, who were included in a screening program for lung disease with a baseline chest radiograph (CR) and complete pulmonary function tests (PFTs). In those patients with lung abnormalities on the CR or PFTs, a high-resolution chest computed tomography scan (HRCT) was performed. We included 40 patients (30 women). Altered PFTs were detected in 18 (45%) of these patients. These cases had a diffusion lung transfer capacity of carbon monoxide (DLCO) of <80% of predicted, without a significant reduction in the forced vital capacity. The HRCT detected abnormalities in 11 of the 18 patients. Diffuse bronchiectasis was the main finding. An inverse correlation between the anti-citrullinated peptide antibody (ACPA) levels and DLCO was found. Asymptomatic lung disease is present in up to 45% of early RA patients and can be determined by PFTs and ACPA levels.
Lorenzin, M; Ortolan, A; Vio, S; Favero, M; Oliviero, F; Zaninotto, M; Cosma, C; Lacognata, C; Punzi, L; Ramonda, R
The study aimed to evaluate biomarkers facilitating early diagnosis of axial spondyloarthritis (axSpA) and correlations between them and disease activity parameters and imaging indexes. Patients with low back pain (LBP) (≥3 months, ≤2 years, onset ≤45 years) participating in the Italian arm of the SpondyloArthritis-Caught-Early SPACE study underwent a physical examination, questionnaires, laboratory tests, X-rays and MRI of the spine and sacroiliac joints (SIJ). An expert rheumatologist formulated axSpA diagnosis in accordance with Assessment of SpondyloArthritis International Society (ASAS) criteria. Disease activity and physical functioning were assessed using imaging, clinical and serological indices. Spine and SIJ MRI and X-rays were scored independently by 2 readers using the SPARCC, mSASSS and NY-criteria. Patients were classified as: subjects with signs of radiographic sacroiliitis (r-axSpA), subjects with signs of sacroiliitis on SIJ-MRI but not on X-rays (nr-axSpA MRI SIJ+) or subjects with no signs of sacroiliitis on MRI/X-rays but with >2 SpA features and signs of bone oedema on MRI spine (nr-axSpA MRI SIJ-/undifferentiated SpA). Significant differences were found in the prevalence of radiographic sacroiliitis, active sacroiliitis on MRI and SPARCC SIJ scores. Biomarker levels were not significantly increased in any of the patient groups. The correlations between IL-17 and IL-23 and other indices were not significant; correlations were found between IL-22 and BASFI, BASG1, HAQ, VAS pain, between mSASSS and MMP3, and between the latter and hsCRP. Although not significantly higher in any of the three groups, IL-22, MMP3 and hsCRP values were correlated with some disease activity indexes and with mSASSS. Large observational studies are required to confirm these preliminary findings.
Cutolo, Maurizio; Villaggio, Barbara; Brizzolara, Renata; Montagna, Paola; Gallo, Fabio; Moretti, Stefano; Bonassi, Stefano; Sulli, Alberto; Soldano, Stefano
The present study evaluates the effects of combined leflunomide (LEF) and low dose of prednisone therapy, on selected inflammatory gene expression in peripheral blood mononuclear cells (PBMCs) of early rheumatoid arthritis (ERA) patients by gene microarray analysis and quantitative real time-polymerase chain reaction (qRT-PCR). Ten ERA patients (mean age 53 ± 10 years) were assigned as untreated (group 1) or pre-treated (group 2) with prednisone (5 mg/day for 3 months) after informed consent and ethics committee approval. Five sex- and age-matched healthy subjects were used as controls (CNT). RNA was extracted by PBMCs, amplified, labelled and hybridised on inflammation DualChip microarray. The expression ratio of 282 inflammatory genes between CNT and ERA patients, before (T0) and after 12 weeks (T1) of combined therapy was detected. qRT-PCR was performed on 7 selected inflammatory RA-related genes (STAT4, MAPK9, HIF1A, MIF, STAT6, NFKB1, TNFRSF1B). At T0, microarray analysis showed 34 altered genes in both ERA groups when compared to CNT (vs. CNT). Seven RA-related genes, investigated in further details, were found up-regulated in group 1 and down-regulated or unchanged in group 2 vs. CNT. At T1, combined therapy induced the down-regulation of these genes in both groups vs. CNT as also confirmed by qRT-PCR performed on selected genes. Untreated ERA patients seem characterised by up-regulation of specific genes involved both in the resistance/inhibition to apoptosis and in the stimulation of pro-inflammatory cytokine production by immune inflammatory cells. Combined LEF and low dose of prednisone therapy seems to play synergistic effects on down-regulation of these genes.
Svensson, Annemarie Lyng; Løgstrup, Brian Bridal; Giraldi, Annamaria; Graugaard, Christian; Blegvad, Jesper; Thygesen, Tina; Sheetal, Ekta; Svendsen, Lone; Emmertsen, Henrik
Introduction Cardiovascular morbidity is a major burden in patients with rheumatoid arthritis (RA). In this study, we compare the effect of a targeted, intensified, multifactorial intervention with that of conventional treatment of modifiable risk factors for cardiovascular disease (CVD) in patients with early RA fulfilling the 2010 American College of Rheumatology European League Against Rheumatism (ACR/EULAR) criteria. Methods and analysis The study is a prospective, randomised, open label trial with blinded end point assessment and balanced randomisation (1:1) conducted in 10 outpatient clinics in Denmark. The primary end point after 5 years of follow-up is a composite of death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke and cardiac revascularisation. Secondary outcomes are: the proportion of patients achieving low-density lipoprotein cholesterol <2.5 mmol/L, glycated haemoglobin <48 mmol/mol, blood pressure <140/90 mm Hg for patients without diabetes and <130/80 mm Hg for patients with diabetes and normoalbuminuria (urinary albumin creatinine ratio <30 mg/g) after 1 year of follow-up and the proportion of patients in each treatment group achieving low RA disease activity after 1 year, defined as a disease activity score C-reactive protein (DAS28-CRP) <3.2 and a DAS28-CRP score <2.6 after 12, 24 and 60 months. Furthermore, all hospitalisations for acute and elective reasons will be adjudicated by the event committee after 12, 24 and 60 months. Three hundred treatment-naive patients with early RA will be randomly assigned (1:1) to receive either conventional treatment administered and monitored by their general practitioner according to national guidelines (control group) or a stepwise implementation administered and monitored in a quarterly rheumatological nurse-administered set-up of behaviour modification and pharmacological therapy targeting (1) hyperlipidaemia, (2) hypertension, (3) hyperglycaemia
Siemons, Liseth; ten Klooster, Peter M.; Vonkeman, Harald E.; van de Laar, Mart A. F. J.; Glas, Cees A. W.
Background The 28-joint Disease Activity Score (DAS28) combines scores on a 28-tender and swollen joint count (TJC28 and SJC28), a patient-reported measure for general health (GH), and an inflammatory marker (either the erythrocyte sedimentation rate [ESR] or the C-reactive protein [CRP]) into a composite measure of disease activity in rheumatoid arthritis (RA). This study examined the reliability of the DAS28 in patients with early RA using principles from generalizability theory and evaluated whether it could be increased by adjusting individual DAS28 component weights. Methods Patients were drawn from the DREAM registry and classified into a “fast response” group (N = 466) and “slow response” group (N = 80), depending on their pace of reaching remission. Composite reliabilities of the DAS28-ESR and DAS28-CRP were determined with the individual components' reliability, weights, variances, error variances, correlations and covariances. Weight optimization was performed by minimizing the error variance of the index. Results Composite reliabilities of 0.85 and 0.86 were found for the DAS28-ESR and DAS28-CRP, respectively, and were approximately equal across patients groups. Component reliabilities, however, varied widely both within and between sub-groups, ranging from 0.614 for GH (“slow response” group) to 0.912 for ESR (“fast response” group). Weight optimization increased composite reliability even further. In the total and “fast response” groups, this was achieved mostly by decreasing the weight of the TJC28 and GH. In the “slow response” group, though, the weights of the TJC28 and SJC28 were increased, while those of the inflammatory markers and GH were substantially decreased. Conclusions The DAS28-ESR and the DAS28-CRP are reliable instruments for assessing disease activity in early RA and reliability can be increased even further by adjusting component weights. Given the low reliability and weightings of the general health
Biliavska, Iuliia; Stamm, Tanja A; Martinez-Avila, Jose; Huizinga, Thomas W J; Landewé, Robert B M; Steiner, Günter; Aletaha, Daniel; Smolen, Josef S; Machold, Klaus P
Objective Performance of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) criteria was analysed in an internationally recruited early arthritis cohort (≤16 weeks symptom duration) enrolled in the ‘Stop-Arthritis-Very-Early’ trial. This sample includes patients with a variety of diseases diagnosed during follow-up. Methods Two endpoints were defined: Investigators’ diagnosis and disease-modifying antirheumatic drug (DMARD) treatment start during the 12-month follow-up. The 2010 criteria were applied to score Patients’ baseline data. Sensitivity, specificity, predictive values and areas under the receiver operating curves of this scoring with respect to both endpoints were calculated and compared to the 1987 criteria. The optimum level of agreement between the endpoints and the 2010 classification score ways estimated by Cohen’s ϰ coefficients. Results 303 patients had 12-months follow-up. Positive predictive values of the 2010 criteria were 0.68 and 0.71 for RA-diagnosis and DMARD-start, respectively. Sensitivity for RA-diagnosis was 0.85, for DMARD-start 0.8, whereas the 1987 criteria’s sensitivities were 0.65 and 0.55. The areas under the receiver operating curves of the 2010 criteria for RA-diagnosis and DMARD-start were 0.83 and 0.78. Analysis of inter-rater-agreement using Cohen’s ϰ demonstrated the highest ϰ values (0.5 for RA-diagnosis and 0.43 for DMARD-start) for the score of 6. Conclusions In this international very early arthritis cohort predictive and discriminative abilities of the 2010 ACR/EULAR classification criteria were satisfactory and substantially superior to the ‘old’ 1987 classification criteria. This easier classification of RA in early stages will allow targeting truly early disease stages with appropriate therapy. PMID:22984174
Contreras-Yáñez, Irazú; Pascual-Ramos, Virginia
Benefits of disease-modifying anti-rheumatic drugs (DMARD) in early rheumatoid arthritis patients (ERAP) will be achieved if patients follow prescribed treatment. Objective was to investigate whether timing of first non-persistence period and/or duration of persistence during the first 4 years of follow-up predicted disease outcomes at the 5(th) year in a cohort of ERAP, initiated in 2004. Up to February 2015, charts of 107 ERAP with at least 5 years of follow-up and prospective 6-month assessments of disease activity, disability and persistence were reviewed. Non-persistence was defined as omission of DMARD and/or corticosteroids for at least 7 consecutive days; regarding methotrexate, one weekly missing dose was considered non-persistence. Persistence was recorded through an interview (up to 2008) and thereafter through a questionnaire; persistence duration was recorded in months of continuous medicationtaking. At the 5(th) year, disease activity was defined according to Disease Activity Score (DAS)28, and disability according to Health Assessment Questionnaire (HAQ). Descriptive statistics and linear and Cox regression analyses were used. At study entry, patients were more frequently middle-aged (39.1 ± 13.3 years) and female (88.8%), as well as more likely to have high disease activity and disability. Over the first 4 years of follow-up, 54.2% of the patients had indications for oral corticosteroids and all traditional DMARDs. Almost 70% had at least one period of non-persistence, and their follow-up (median, 25th-75th interquartile range) to first non-persistence period was 13 months (1-31). Persistence duration during the first 4 years predicted subsequent DAS28 (in addition to gender and baseline DAS28) and HAQ (in addition to age). During the 5(th) year, 68 patients (56 women) achieved sustained remission (DAS28 < 2.6). In female population (n = 95), baseline DAS28 (odds ratio [OR], 0.65; 95 % confidence interval [CI], 0.50-0.83; p = 0
Akdemir, Gülşah; Heimans, Lotte; Bergstra, Sytske Anne; Goekoop, Robbert J; van Oosterhout, Maikel; van Groenendael, Johannes H L M; Peeters, André J; Steup-Beekman, Gerda M; Lard, Leroy R; de Sonnaville, Peter B J; Grillet, Bernard A M; Huizinga, Tom W J; Allaart, Cornelia F
To determine the 5-year outcomes of early remission induction therapy followed by targeted treatment aimed at drug-free remission (DFR) in patients with early arthritis. In 12 hospitals, 610 patients with early (<2 years) rheumatoid arthritis (RA) or undifferentiated arthritis (UA) started on methotrexate (MTX) 25 mg/week and prednisone (60 mg/day tapered to 7.5 mg/day). Patients not in early remission (Disease Activity Score <1.6 after 4 months) were randomised (single blind) to arm 1, adding hydroxychloroquine 400 mg/day and sulfasalazine 2000 mg/day, or arm 2, switching to MTX plus adalimumab 40 mg/2 weeks. Treatment adjustments over time aimed at DFR. Outcomes were remission percentages, functional ability, toxicity and radiological damage progression after 5 years. After 4 months, 387 patients were in early remission, 83 were randomised to arm 1 and 78 to arm 2. After 5 years, 295/610 (48%) patients were in remission, 26% in sustained DFR (SDFR) (≥1 year) (220/387 (57%) remission and 135/387 (35%) SDFR in the early remission group, 50% remission, 11% SDFR in the randomisation arms without differences between the arms). More patients with UA (37% vs 23% RA, p=0.001) and more anticitrullinated protein antibody (ACPA)-negative patients (37% vs 18% ACPA-positive, p<0.001) achieved SDFR.Overall, mean Health Assessment Questionnaire was 0.6 (0.5), and median (IQR) damage progression was 0.5 (0-2.7) Sharp/van der Heijde points, with only five patients showing progression >25 points in 5 years. Five years of DFR-steered treatment in patients with early RA resulted in almost normal functional ability without clinically relevant joint damage across treatment groups. Patients who achieved early remission had the best clinical outcomes. There were no differences between the randomisation arms. SDFR is a realistic treatment goal. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved
Rannio, Tuomas; Asikainen, Juha; Kokko, Arto; Hannonen, Pekka; Sokka, Tuulikki
We analyzed remission rates at 3 and 12 months in patients with rheumatoid arthritis (RA) who were naive for disease-modifying antirheumatic drugs (DMARD) and who were treated in a Finnish rheumatology clinic from 2008 to 2011. We compared remission rates and drug treatments between patients with RA and patients with undifferentiated arthritis (UA). Data from all DMARD-naive RA and UA patients from the healthcare district were collected using software that includes demographic and clinical characteristics, disease activity, medications, and patient-reported outcomes. Our rheumatology clinic applies the treat-to-target principle, electronic monitoring of patients, and multidisciplinary care. Out of 409 patients, 406 had data for classification by the 2010 RA criteria of the American College of Rheumatology/European League Against Rheumatism. A total of 68% were female, and mean age (SD) was 58 (16) years. Respectively, 56%, 60%, and 68% were positive for anticyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF), and RF/anti-CCP, and 19% had erosive disease. The median (interquartile range) duration of symptoms was 6 (4-12) months. A total of 310 were classified as RA and 96 as UA. The patients with UA were younger, had better functional status and lower disease activity, and were more often seronegative than the patients with RA. The 28-joint Disease Activity Score (3 variables) remission rates of RA and UA patients at 3 months were 67% and 58% (p = 0.13), and at 12 months, 71% and 79%, respectively (p = 0.16). Sustained remission was observed in 57%/56% of RA/UA patients. Patients with RA used more conventional synthetic DMARD combinations than did patients with UA. None used biological DMARD at 3 months, and only 2.7%/1.1% of the patients (RA/UA) used them at 12 months (p = 0.36). Remarkably high remission rates are achievable in real-world DMARD-naive patients with RA or UA.
Landewé, Robert B M; Boers, Maarten; Verhoeven, Arco C; Westhovens, Rene; van de Laar, Mart A F J; Markusse, Harry M; van Denderen, J Christiaan; Westedt, Marie Louise; Peeters, Andre J; Dijkmans, Ben A C; Jacobs, Piet; Boonen, Annelies; van der Heijde, Désirée M F M; van der Linden, Sjef
The Combinatietherapie Bij Reumatoide Artritis (COBRA) trial demonstrated that step-down combination therapy with prednisolone, methotrexate, and sulfasalazine (SSZ) was superior to SSZ monotherapy for suppressing disease activity and radiologic progression of rheumatoid arthritis (RA). The current study was conducted to investigate whether the benefits of COBRA therapy were sustained over time, and to determine which baseline factors could predict outcome. All patients had participated in the 56-week COBRA trial. During followup, they were seen by their own rheumatologists and were also assessed regularly by study nurses; no treatment protocol was specified. Disease activity, radiologic damage, and functional ability were the primary outcome domains. Two independent assessors scored radiographs in sequence according to the Sharp/van der Heijde method. Outcomes were analyzed by generalized estimating equations on the basis of intent-to-treat, starting with data obtained at the last visit of the COBRA trial (56 weeks after baseline). At the beginning of followup, patients in the COBRA group had a significantly lower mean time-averaged 28-joint disease activity score (DAS28) and a significantly lower median radiologic damage (Sharp) score compared with those in the SSZ monotherapy group. The functional ability score (Health Assessment Questionnaire [HAQ]) was similar in both groups. During the 4-5 year followup period, the time-averaged DAS28 decreased 0.17 points per year in the SSZ group and 0.07 in the COBRA group. The Sharp progression rate was 8.6 points per year in the SSZ group and 5.6 in the COBRA group. After adjustment for differences in treatment and disease activity during followup, the between-group difference in the rate of radiologic progression was 3.7 points per year. The HAQ score did not change significantly over time. Independent baseline predictors of radiologic progression over time (apart from treatment allocation) were rheumatoid factor
Marcos, Josefina; Waimann, Christian; Dal Pra, Fernando; Hogrefe, Jimena; Retamozo, Soledad; Caeiro, Francisco; Casalla, Luciana; Benegas, Mariana; Rillo, Oscar; Spindler, Alberto; Berman, Horacio; Berman, Alberto; Secco, Anastasia; García Salinas, Rodrigo; Catalán Pellet, Antonio; Ceccato, Federico; Paira, Sergio; Marcos, Juan C; Maldonado Cocco, José A; Citera, Gustavo
The aim of the present study is to describe the general characteristics of a cohort of patients with early arthritis in Argentina. CONAART (Consorcio Argentino de Artritis Temprana--Argentine Consortium for Early Arthritis) is an initiative of seven rheumatology centres across Argentina. Patients were included if they had at least one or more swollen joints and <2 years of disease duration. Social, demographic, familiar, hereditary, clinical and laboratory data were recollected. At first visit and every year, X-rays of hands and feet were performed and working characteristics and pharmaco-economic data were re-collected. A total of 413 patients were included. Of them, 327 (79.2%) were women with a median age of 49 years and a median disease duration of 6 months. Of the total, 183 (44.3%) had RA (ACR 1987) and 167 (40.4%) undifferentiated arthritis (UA). Other diagnoses included: 12 crystalics, 11 PsA, 6 uSpA, 6 other CTD, 1 AS and 27 other diagnosis. As 85% of our population had RA and UA, we only compared these two groups of patients. Patients with RA had significantly worse activity parameters of the disease (DAS of 28 joints), functional capacity (HAQ) and quality of life (Rheumatoid Arthritis Quality of Life) than patients with UA. The frequency of RF and anti-CCP, and symmetrical distribution were also significantly higher in patients with RA compared with UA patients. All patients with RA initiated early specific treatment, in a period no longer than 6 months from the beginning of the disease. Early arthritis clinics are a useful tool to identify and treat patients with different forms of joint involvement.
Jacoby, R. K.; Jayson, M. I. V.; Cosh, J. A.
One hundred patients with “definite” or “classical” rheumatoid arthritis were followed in a hospital clinic from within one year of the onset of the arthritis. The average interval between onset and first attendance was 3·7 months. Onset was commoner in the winter, transient prodromal symptoms being noted in 23, with possible precipitating factors in 14. The serum rheumatoid factor test was positive at some time in 88. The patients were reassessed between eight and 14 years later. Seventeen died during this period, five possibly as a result of the disease or its treatment. The remaining patients had improved as a whole in terms of the blood sedimentation rate, haemoglobin, titre of the rheumatoid factor test, and status of the disease, but there was an overall deterioration in functional capacity. Both the rheumatoid factor titre and the functional capacity at an earlier review could be directly correlated with the outcome, but other factors were not found to influence the ultimate prognosis. PMID:4700332
Plant, Darren; Thomson, Wendy; Lunt, Mark; Flynn, Edward; Martin, Paul; Eyre, Steven; Farragher, Tracey; Bunn, Diane; Worthington, Jane; Symmons, Deborah
Objectives. Recent whole-genome and candidate gene association studies in RA have identified a number of single nucleotide polymorphisms (SNPs) that predispose to disease with moderate risk. It remains poorly understood how recently identified genetic factors may contribute to RA severity. We therefore sought to investigate the role of recently identified RA susceptibility SNP markers in predicting erosive outcome in patients with recent-onset inflammatory polyarthritis (IP). Methods. DNA and X-ray data were available for 1049 patients who were registered between 1990 and 2003 with the Norfolk Arthritis Register (NOAR); a primary care-based inception cohort of patients with recent-onset IP. Demographic and clinical data were recorded at inclusion, and at yearly assessments thereafter. Patients were genotyped for 18 SNP markers. The presence of serum anti citrullinated peptide antibodies (ACPAs) was assessed in samples collected at inclusion to the NOAR. The association of serological and genetic markers with poor radiological (Larsen) score at Years 1 and 5, and erosions at Years 1 and 5 was investigated. Results. Baseline ACPA positivity was associated with erosive disease and higher radiological damage. SNP markers within the TRAF1/C5 locus were associated with erosive disease at Year 1 [rs2900180: odds ratio (OR) 1.53 (95% CI 1.14, 2.05)] and Year 5 [rs2900180: OR 1.47 (95% CI 1.07, 2.02)]. None of the SNP markers tested was associated with Larsen score. Conclusion. Our results are in keeping with a previous report and suggest that the TRAF1/C5 region is associated with risk of development of radiological erosions in IP/RA patients. The finding requires replication in other large data sets. PMID:20219786
Gwinnutt, James M; Symmons, Deborah P M; MacGregor, Alexander J; Chipping, Jacqueline R; Lapraik, Chloe; Marshall, Tarnya; Lunt, Mark; Verstappen, Suzanne M M
To analyse predictors and outcomes of major orthopaedic surgery in a cohort of RA patients followed for 20 years. Patients were recruited to the Norfolk Arthritis Register from 1990 to 1994. Demographic and clinical variables (including the HAQ and swollen and tender joint counts) were assessed at baseline; the 2010 ACR/EULAR RA classification criteria were applied. Patients reported incident comorbidities and major orthopaedic joint surgery (replacement, synovectomy, fusion, excision) when reassessed at years 1, 2, 3, 5, 7, 10, 15 and 20. Baseline and time-varying predictors of orthopaedic surgery were assessed using a conditional risk set model, a type of multiple-failure survival analysis. Change in disability after surgery was assessed using weighted mixed-effects linear regression. Of 589 RA patients [median age 56 years (IQR 45-68); 66.7% women] recruited to the Norfolk Arthritis Register with at least one follow-up, 102 reported a total of 180 major surgeries, with hip replacement being the most common (n = 68/180). Patients reporting major surgery had worse functional disability at all time points, but similar swollen/tender joint counts to those without major surgery. Each unit increase in HAQ score was associated with a doubling of the patient's risk of having surgery by the next assessment [hazard ratio 2.11 per unit increase in HAQ (95% CI 1.64, 2.71)]. Patients had worse HAQ scores after surgery than patients not undergoing surgery [β = 0.17 (95% CI 0.03, 0.32)]. HAQ was the strongest predictor of future major surgery. This supports the argument that HAQ should be included in routine clinical assessment.
Courbon, Guillaume; Cleret, Damien; Linossier, Marie-Thérèse; Vico, Laurence; Marotte, Hubert
Synovitis is usually observed before loss of articular function in rheumatoid arthritis (RA). In addition to the synovium and according to the "Inside-Outside" theory, bone compartment is also involved in RA pathogenesis. Then, we investigated time dependent articular bone loss and prediction of early bone loss to late arthritis severity on the rat adjuvant-induced arthritis (AIA) model. Lewis female rats were longitudinally monitored from arthritis induction (day 0), with early (day 10) and late (day 17) steps. Trabecular and cortical microarchitecture parameters of four ankle bones were assessed by microcomputed tomography. Gene expression was determined at sacrifice. Arthritis occurred at day 10 in AIA rats. At this time, bone erosions were detected on four ankle bones, with cortical porosity increase (+67%) and trabecular alterations including bone volume fraction (BV/TV: -13%), and trabecular thickness decrease. Navicular bone assessment was the most reproducible and sensitive. Furthermore, strong correlations were observed between bone alterations at day 10 and arthritis severity or bone loss at day 17, including predictability of day 10 BV/TV to day 17 articular index (R(2) = 0.76). Finally, gene expression at day 17 confirmed massive osteoclast activation and interestingly provided insights on strong activation of bone formation inhibitor markers at the joint level. In rat AIA, bone loss was already observed at synovitis onset and was predicted late arthritis severity. Our results reinforced the key role of subchondral bone in arthritis pathogenesis, in favour to the "Inside-Outside" theory. Mechanisms of bone loss in rat AIA involved resorption activation and formation inhibition changes. J. Cell. Physiol. 232: 1318-1325, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Rizzo, Roberta; Farina, Ilaria; Bortolotti, Daria; Galuppi, Elisa; Padovan, Melissa; Di Luca, Dario; Govoni, Marcello
A growing body of evidence indicates a possible involvement of HLA (human leukocyte antigen)-G antigens in rheumatoid arthritis (RA), mainly in the HLA-G dimeric isoform, the most active HLA-G form with the strongest immunosuppression, that showed an excellent anti-inflammatory effect in collagen-induced arthritis model mice. However, the relevance of HLA-G dimers in RA response to methotrexate (MTX) treatment is still unknown. We analyzed the HLA-G dimers' amount in plasma samples from early rheumatoid arthritis (ERA) patients before MTX therapy and evaluated the role of these molecules as biomarker of the different response to the treatment. Plasma sHLA-G levels were detected by ELISA, and HLA-G dimeric and monomeric forms were revealed by Western blot in 12 MTX responder (reaching DAS28 remission <2.6) and 8 MTX non-responder (DAS28 ≥5.1) patients before the therapy. The response to MTX was evaluated after 6 months of treatment. All ERA patients reaching remission showed higher plasma sHLA-G levels and the 78 kDa HLA-G dimeric form. Unresponsive ERA patients were characterized by lower plasma sHLA-G levels, and only one patient presented the 78 kDa HLA-G dimeric form (DAS28 5.1). Our preliminary results support the hypothesis that in ERA patients, sHLA-G and, in particular, the presence of the dimeric form in plasma samples before MTX therapy could be an a priori biomarker for the response to MTX treatment.
In patients with early rheumatoid arthritis, the new ACR/EULAR definition of remission identifies patients with persistent absence of functional disability and suppression of ultrasonographic synovitis.
Sakellariou, Garifallia; Scirè, Carlo Alberto; Verstappen, Suzanne M M; Montecucco, Carlomaurizio; Caporali, Roberto
To test the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) and disease activity score in 44 and 28 joints (DAS, DAS28) definitions of remission in early rheumatoid arthritis (RA), against disability and ultrasound-detectable synovitis. In an observational study of early RA patients, remission rates were determined and compared in 166 patients. The remission definitions included the simplified disease activity index (SDAI≤3.3), ACR/EULAR (categorical), DAS28 (<2.6) and DAS (<1.6). The health assessment questionnaire (HAQ) was completed at baseline and 12 months, power Doppler-positive synovitis (PDPS) was assessed at baseline, 6 and 12 months. Cross-sectionally, the outcomes were low functional disability (HAQ≤0.5) or absent PDPS in all joints, while longitudinally the outcomes were stable low functional disability and persistent absent PDPS in all joints. At baseline, 33.7% of patients achieved DAS28 remission, 43.37% DAS remission, 16.8% SDAI remission, 13.8% ACR/EULAR remission. DAS28, SDAI and ACR/EULAR remission was cross-sectionally associated with low functional disability and absent PDPS. All definitions were longitudinally associated with low functional disability: positive likelihood ratios (LR+) of 3.24 for DAS28, 2.14 for DAS, 4.86 for SDAI, 5.67 for ACR/EULAR criteria, and with absent PDPS for DAS28 (LR+ 1.66), SDAI (LR+ 6.46), ACR/EULAR (LR+ 5.07). The new remission definitions confirmed their validity in an observational setting and identify patients with better disease control.
Early prediction of rheumatoid arthritis by magnetic resonance imaging in the absence of anti-cyclic citrullinated peptide antibodies and radiographic erosions in undifferentiated inflammatory arthritis patients: a prospective study.
Ji, Lanlan; Li, Guangtao; Xu, Yufeng; Zhou, Wei; Zhang, Zhuoli
To assess the practicability of magnetic resonance imaging (MRI) in confirming the diagnosis of clinically suspected rheumatoid arthritis (RA), when anti-cyclic citrullinated peptide antibody and radiographic erosions are absent. We prospectively involved 31 treatment-naive patients with early inflammatory arthritis. At the initial visit, X-rays and gadolinium-enhanced MRI of both hands, as well as serological examinations and acute phase reactants were performed. The scores of synovitis, bone edema, bone erosion and tenosynovitis of metacarpophalangeal and wrist joints were evaluated using the RA-MRI scoring system. For all the patients, radiographs at baseline were normal and anti-cyclic citrullinated peptide antibodies were negative. At the end of follow-up(median 15 months, range 12-20 months), 22 patients were diagnosed as having RA according to 1987 American College of Rheumatology criteria. Bone edema, erosions, synovitis and tenosynovitis were observed in all the patients. However, the frequency of symmetric synovitis in wrists was significantly higher in the RA group. Moreover this group turned out to have significantly higher MRI bone erosion score in wrists. Further, receiver operating characteristic curve analysis revealed a positive wrist bone erosion score at 5, with a specificity of 78% and a sensitivity of 68%. There was no significant difference between the two groups with respect to metacarpophalangeal synovitis, metacarpophalangeal bone erosion, bone edema or tenosynovitis. MRI evidence of symmetric synovitis at wrist and a high bone erosion score at that site may assist in making an early diagnosis of RA in those patients who are negative for anti-cyclic citrullinated peptide antibody. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.
Effect of early treatment on physical function in daily management of rheumatoid arthritis: a 5-year longitudinal study of rheumatoid arthritis patients in the National Database of Rheumatic Diseases in Japan.
Hirata, Akie; Suenaga, Yasuo; Miyamura, Tomoya; Matsui, Toshihiro; Tohma, Shigeto; Suematsu, Eiichi; Ohnaka, Keizo; Takayanagi, Ryoichi
The purpose of this study was to assess 5-year changes in physical function and factors associated with improvement among patients with rheumatoid arthritis (RA) in daily clinical practice, focusing on the effect of treatments, including biologic agents, in the early stage of disease course. The National Database of Rheumatic Diseases by iR-net in Japan (NinJa) was searched for patients with disease duration ≤ 2 years and modified health assessment questionnaire (mHAQ) > 0 between 2004 and 2007, so that 510 patients were included in the final analysis. Multivariate-logistic regression analyses were used to identify predictors of 5-year mHAQ disability score improvement. Median mHAQ score was 0.40 at baseline and decreased to a median 0.17 after 5 years. Seventy-four percent of the patients were treated with methotrexate (MTX) and 25% with biologic agents, with early use of biologic agents (within 2 years of RA onset) increasing over time. Multivariate analyses identified higher baseline Disease Activity Score of 28 joints - C-reactive protein and early use of MTX (within 1 year of RA onset) and of biologic agents (within 2 years) as significantly associated with improved mHAQ; odds ratios of the early treatment were 1.83 (P = 0.01) for MTX and 2.23 (P = 0.04) for biologic agents, respectively. Five-year mHAQ improved in early RA patients in the NinJa database. In daily clinical management of RA, likewise in clinical trials, early administration of MTX or biologic agents is able to improve physical function outcome. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.
Wevers-de Boer, Kirsten V C; Heimans, Lotte; Visser, Karen; Schouffoer, Anne A; Molenaar, Esmeralda T H; van Groenendael, Johannes H L M; Peeters, André J; Speyer, Irene; Collée, Gerard; Huizinga, Tom W J; Allaart, Cornelia F
The aim of this study was to assess whether baseline characteristics in patients with undifferentiated arthritis or early RA affect the possibility of achieving drug-free remission after 1 year (DFR1 year) of early remission induction therapy. We included 375 patients participating in the IMPROVED study who achieved remission (DAS < 1.6) after 4 months (early remission) and were by protocol able to achieve DFR1 year. Having started with MTX plus prednisone, patients tapered prednisone to zero; after 8 months, those still in remission tapered MTX to zero, while those not in remission restarted prednisone. Characteristics of patients achieving and not achieving DFR1 year were compared. Logistic regression was performed to identify predictors of DFR1 year. After 1 year, 119 patients (32%) were in DFR. Presence of RF, fulfilling the 2010 criteria for RA, and a low tender joint count were associated with achieving DFR1 year, whereas presence of ACPA was not. None of the baseline characteristics was independently associated with DFR1 year. DFR1 year was sustained for 4 months in 65% of the patients. ACPA-positive patients less often had sustained DFR than ACPA-negative patients (58% vs 80%, P = 0.013). After 1 year of remission-steered treatment, 32% of the patients who had achieved early remission after 4 months were able to taper medication and achieved DFR. Neither the presence of ACPA nor any other baseline characteristics were independently associated with achieving DFR1 year, but in ACPA-positive patients DFR was less often sustained. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: firstname.lastname@example.org.
Lard, L R; Boers, M; Verhoeven, A; Vos, K; Visser, H; Hazes, J M W; Zwinderman, A H; Schreuder, G M T; Breedveld, F C; De Vries, R R P; van der Linden, S; Zanelli, E; Huizinga, T W J
The presence of certain HLA class II antigens is strongly associated with the progression of joint destruction in rheumatoid arthritis (RA). Such antigens may be more effective than other class II antigens in inducing the formation of autoreactive T cells after presentation of (auto)antigens. We investigated whether early and aggressive treatment with disease-modifying antirheumatic drugs could modify this relationship. We analyzed data from 2 studies of patients with early RA treated according to different strategies. The first study consisted of 2 cohorts, one (n = 109; median disease duration before treatment 4 months) was treated according to the pyramid strategy (initial nonsteroidal antiinflammatory drugs, followed by chloroquine [CQ] or sulfasalazine [SSZ] when necessary), and the other (n = 97; median disease duration before treatment 2 weeks) was immediately treated with CQ or SSZ. The second study comprised 155 patients (median disease duration 4 months) from the Combinatietherapie Bij Reumatoide Artritis (COBRA) trial, in which patients were randomly assigned to combination treatment with step-down prednisolone, methotrexate (MTX), and SSZ (n = 76) or with SSZ alone (n = 79). Prednisolone and MTX dosages were tapered and stopped after 28 and 40 weeks, respectively. The extent of joint damage was measured by the modified Sharp method. In the pyramid treatment cohort, the median increase in Sharp score after 2 years was 12 in patients positive for the shared epitope (SE) and 1 in SE- patients. In the immediate treatment cohort, the median increase was 3 in SE+ patients and 2 in SE- patients. In the SSZ group of the COBRA study, the median increase in Sharp score after 1 year was 11 in DR4+ patients and 3 in DR4- patients. In the combination treatment group, the median increase was 4 in DR4+ patients and 2 in DR4- patients. Significance was confirmed by multiple regression using log-transformed scores. Early and aggressive antirheumatic drug treatment
Jones, V E; Jacoby, R K; Wallington, T; Holt, P
Fifty-three patients with early arthritis were studied longitudinally for up to 3 years. During this time, 24 developed sufficient features for definite rheumatoid arthritis (RA) to be diagnosed. The other (arthralgia patients) differed from the RA patients as, in the majority, C-reactive protein and ESR were normal and anti-nuclear antibodies or rheumatoid factors were rarely found. Moreover, in time their signs and symptoms improved or disappeared. Circulating immune complexes were detected in both groups of patients by the platelet aggregation test whereas complexes detected by abnormal Clq-binding activity were found mainly in the RA patients. Platelet-aggregating complexes were usually present in the first samples studied and disappeared in the arthralgia patients with recovery from their symptoms. In the RA patients, Clq-binding complexes appeared simultaneously or later than platelet-aggregating complexes but both tests were positive several months before RA could be diagnosed. These results suggest that immune complexes are one of the first immunological abnormalities to appear in patients with arthritis. Although the constituent antigen and antibody of complexes detected by either test are unknown, their possible nature is discussed. PMID:6976861
Akdemir, G; Markusse, I M; Goekoop-Ruiterman, Y P M; Steup-Beekman, G M; Grillet, B A M; Kerstens, P J S M; Lems, W F; Huizinga, T W J; Allaart, C F
To compare rheumatologists' adherence to treatment protocols for rheumatoid arthritis (RA) targeted at Disease Activity Score (DAS) ≤2.4 or <1.6. The BeSt-study enrolled 508 early RA (1987) patients targeted at DAS ≤2.4. The IMPROVED-study included 479 early RA (2010) and 122 undifferentiated arthritis patients targeted at DAS <1.6. We evaluated rheumatologists' adherence to the protocols and assessed associated opinions and conditions during 5 years. Protocol adherence was higher in BeSt than in IMPROVED (86 and 70 %), with a greater decrease in IMPROVED (from 100 to 48 %) than in BeSt (100 to 72 %). In BeSt, 50 % of non-adherence was against treatment intensification/restart, compared to 63 % in IMPROVED and 50 vs. 37 % were against tapering/discontinuation. In both studies, non-adherence was associated with physicians' disagreement with DAS or with next treatment step and if patient's visual analogue scale (VAS) for general health was ≥20 mm higher than the physician's VAS. In IMPROVED, also discrepancies between swelling, pain, erythrocyte sedimentation rate, and VASgh were associated with non-adherence. Adherence to DAS steered treatment protocols was high but decreased over 5 years, more in a DAS <1.6 steered protocol. Non-adherence was more likely if physicians disagreed with DAS or next treatment step. In the DAS <1.6 steered protocol, non-adherence was also associated with discrepancies between subjective and (semi)objective disease outcomes, and often against required treatment intensification. These results may indicate that adherence to DAS-steered protocols appears to depend in part on the height of the target and on how physicians perceive the DAS reflects RA activity.
Pascual-Ramos, Virginia; Contreras-Yáñez, Irazú; Villa, Antonio R; Cabiedes, Javier; Rull-Gabayet, Marina
Introduction Aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) plays a major role in improving early rheumatoid arthritis (RA) patient outcomes. Persistence and adherence with medication occurs variably (20% to 70%). The objectives of the study were to determine medication persistence (MP) in early RA patients over 13 consecutive visits each 2 months apart, to investigate the relationship between MP and disease activity, disability and structural damage, and to identify baseline prognosticators. Methods Charts from 75 patients of an early RA cohort were reviewed. At each visit, a rheumatologist interviewed patients regarding therapy, scored disease activity with the 28-joint disease activity score (DAS28) and disability with the health assessment questionnaire (HAQ), and recorded comorbidities and treatment. A complete medical history was obtained at baseline. MP was defined as the duration of time from initiation to discontinuation of at least one DMARD and/or corticosteroids for at least 1 week and was reported as a dichotomous variable at consecutive evaluations. Structural damage was defined by detection of new erosions on radiography. Descriptive statistics, Student's t test, the chi-squared test, and logistic regression analyses were used. Results The proportion of MP patients decreased from 98% at 2 months to 34% at 2 years. MP patients (n = 32) had similar DAS28 to non-MP patients (n = 53) at initial visits, lower DAS28 and greater DAS28 improvements at follow-ups (P ≤ 0.05 at visits 4, 6, 7 and 9) and reached sustained remission (≥ 3 consecutive visits with DAS28 < 2.6) more frequently (82.8% versus 46.5%, P = 0.003) and earlier (7.7 ± 4.6 versus 13.6 ± 5.7 months, P = 0.001) than non-MP patients. MP patients had similar baseline HAQ scores, but lower HAQ scores at follow-up (P ≤ 0.05 at visits 3, 5, 6, 7, 9, 10 and 13). More non-MP patients developed erosive disease than MP patients (26.8% versus 17.9%, P = 0.56). Older age
Brinkmann, Gina Hetland; Norli, Ellen S; Bøyesen, Pernille; van der Heijde, Désirée; Grøvle, Lars; Haugen, Anne J; Nygaard, Halvor; Bjørneboe, Olav; Thunem, Cathrine; Kvien, Tore K; Mjaavatten, Maria D; Lie, Elisabeth
To determine how the European League Against Rheumatism (EULAR) definition of erosive disease (erosion criterion) contributes to the number of patients classified as rheumatoid arthritis (RA) according to the 2010 American College of Rheumatology/EULAR RA classification criteria (2010 RA criteria) in an early arthritis cohort. Patients from the observational study Norwegian Very Early Arthritis Clinic with joint swelling ≤16 weeks, a clinical diagnosis of RA or undifferentiated arthritis, and radiographs of hands and feet were included. Erosive disease was defined according to the EULAR definition accompanying the 2010 RA criteria. We calculated the additional number of patients being classified as RA based on the erosion criteria at baseline and during follow-up. Of the 289 included patients, 120 (41.5%) fulfilled the 2010 RA criteria, whereas 15 (5.2%) fulfilled only the erosion criterion at baseline. 118 patients had radiographic follow-up at 2 years, of whom 6.8% fulfilled the 2010 RA criteria and only one patient fulfilled solely the erosion criterion during follow-up. Few patients with early arthritis were classified as RA based on solely the erosion criteria, and of those who did almost all did so at baseline. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Östlund, Gunnel; Björk, Mathilda; Thyberg, Ingrid; Thyberg, Mikael; Valtersson, Eva; Stenström, Birgitta; Sverker, Annette
Psychological distress is a well-known complication in rheumatoid arthritis (RA), but knowledge regarding emotions and their relationship to participation restrictions is scarce. The objective of the study was to explore emotions related to participation restrictions by patients with early RA. In this study, 48 patients with early RA, aged 20-63 years, were interviewed about participation restrictions using the critical incident technique. Information from transcribed interviews was converted into dilemmas and linked to International Classification of Functioning, Disability, and Health (ICF) participation codes. The emotions described were condensed and categorized. Hopelessness and sadness were described when trying to perform daily activities such as getting up in the mornings and getting dressed, or not being able to perform duties at work. Sadness was experienced in relation to not being able to continue leisure activities or care for children. Examples of fear descriptions were found in relation to deteriorating health and fumble fear, which made the individual withdraw from activities as a result of mistrusting the body. Anger and irritation were described in relation to domestic and employed work but also in social relations where the individual felt unable to continue valued activities. Shame or embarrassment was described when participation restrictions became visible in public. Feelings of grief, aggressiveness, fear, and shame are emotions closely related to participation restrictions in everyday life in early RA. Emotions related to disability need to be addressed both in clinical settings in order to optimize rehabilitative multi-professional interventions and in research to achieve further knowledge.
Introduction Cardiovascular disease (CVD) is the leading cause of death in patients with inflammatory polyarthritis (IP), especially in seropositive disease. In established rheumatoid arthritis (RA), insulin resistance (IR) is increased and associated with CVD. We investigated factors associated with IR in an inception cohort of patients with early IP. Methods Patients with early IP (two or more swollen joints for four or more weeks), aged 18 to 65 years, seen within 24 months of symptom onset were recruited from the Norfolk Arthritis Register (NOAR), a primary-care-based inception cohort. Assessment included joint examination, current and prior therapy and completion of the Health Assessment Questionnaire. Fasting blood was taken for measurement of CVD risk factors, rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), C-reactive protein (CRP), and insulin levels. IR was calculated using the homeostatic model assessment (HOMA-IR). We examined factors associated with IR using univariate and multivariable linear regression models. Results A total of 196 patients, including 59 (30%) males, were studied with a median (interquartile range, IQR) age and IP symptom duration of 49 (40 to 57) years and 6.7 (4.6 to 10.7) months, respectively. After age and gender adjustment, HOMA-IR was associated with obesity, (β-Coefficient (95% CI); 1.60 (0.96, 2.24)), higher systolic and diastolic blood pressure (0.03 (0.01, 0.05) and 0.04 (0.01, 0.08) respectively), triglycerides (1.06 (0.54, 1.57)), and HDL (-1.38 (-2.17,-0.58)). HOMA-IR was associated with serological status and this association persisted after adjustment for classic CVD risk factors and other IP-related variables (RF β-Coefficient (95% CI); 0.87 (0.20, 1.53) and ACPA β-Coefficient (95% CI); 1.42 (0.70, 2.15)). Conclusions Seropositivity for RF or ACPA was associated with IR in this early IP cohort. This association may, in part, explain why seropositive patients have excess CVD mortality. PMID
Westhovens, Rene; Robles, Manuel; Ximenes, Antonio Carlos; Wollenhaupt, Jurgen; Durez, Patrick; Gomez-Reino, Juan; Grassi, Walter; Haraoui, Boulos; Shergy, William; Park, Sung-Hwan; Genant, Harry; Peterfy, Charles; Becker, Jean-Claude; Murthy, Bindu
Objectives To evaluate maintenance of response while reducing intravenous abatacept dose from ∼10 mg/kg to ∼5 mg/kg in patients with early rheumatoid arthritis (RA) who achieved disease activity score (DAS)28 (erythrocyte sedimentation rate, ESR) <2.6. Methods This 1-year, multinational, randomised, double-blind substudy evaluated the efficacy and safety of ∼10 mg/kg and ∼5 mg/kg abatacept in patients with early RA with poor prognosis who had reached DAS28 (ESR) <2.6 at year 2 of the AGREE study. The primary outcome was time to disease relapse (defined as additional disease-modifying antirheumatic drugs, ≥2 courses high-dose steroids, return to open-label abatacept ∼10 mg/kg, or DAS28 (C reactive protein) ≥3.2 at two consecutive visits). Results 108 patients were randomised (∼10 mg/kg, n=58; ∼5 mg/kg, n=50). Three and five patients, respectively, discontinued, and four per group returned to open-label abatacept. Relapse over time and the proportion of patients relapsing were similar in both groups (31% (∼10 mg/kg) vs 34% (∼5 mg/kg); HR: 0.87 (95% CI 0.45 to 1.69)). Mean steady-state trough serum concentration for the ∼10 mg/kg group was 20.3–24.1 µg/mL, compared with 8.8–12.0 µg/mL for the ∼5 mg/kg group. Conclusions This exploratory study suggests that abatacept dose reduction may be an option in patients with poor prognosis early RA who achieve DAS28 (ESR) <2.6 after ≥1 year on abatacept (∼10 mg/kg). Trial registration number NCT00989235. PMID:25550337
Desai, Rishi J; Rao, Jaya K; Hansen, Richard A; Fang, Gang; Maciejewski, Matthew; Farley, Joel
To compare the risk of cardiovascular (CV) events between use of tumor necrosis factor-α inhibitors (TNFi) and nonbiologic disease-modifying antirheumatic drugs (DMARD) in patients with early rheumatoid arthritis (RA). A nested case-control study was conducted using data from Truven's MarketScan commercial and Medicare claims database for patients with early RA who started treatment with either a TNFi or a nonbiologic DMARD between January 1, 2008, and December 31, 2010. Date of CV event diagnosis for cases was defined as the event date, and 12 age-matched and sex-matched controls were sampled using incidence density sampling. Drug exposure was defined into the following mutually exclusive categories hierarchically: (1) current use of TNFi (with or without nonbiologics), (2) past use of TNFi (with or without nonbiologics), (3) current use of nonbiologics only, and (4) past use of nonbiologics only. Current use was defined as any use in the period 90 days prior to the event date. Conditional logistic regression models were used to derive incidence rate ratios (IRR). From the cohort of patients with early RA, 279 cases of incident CV events and 3348 matched controls were identified. The adjusted risk of CV events was not significantly different between current TNFi users and current nonbiologic users (IRR 0.92, 95% CI 0.59-1.44). However, past users of nonbiologics showed significantly higher risk compared to current nonbiologic users (IRR 1.47, 95% CI 1.04-2.08). No differences in the CV risk were found between current TNFi and current nonbiologic DMARD treatment in patients with early RA.
O'Dell, James R.; Curtis, Jeffrey R.; Mikuls, Ted R.; Cofield, Stacey S.; Bridges, S. Louis; Ranganath, Veena K.; Moreland, Larry
Objective Methotrexate (MTX) taken as monotherapy is recommended as the initial disease-modifying antirheumatic drug for rheumatoid arthritis (RA). The purpose of this study was to examine outcomes of a blinded trial of initial MTX monotherapy with the option to step-up to combination therapy as compared to immediate combination therapy in patients with early, poor-prognosis RA. Methods In the Treatment of Early Rheumatoid Arthritis (TEAR) trial, 755 participants with early, poor-prognosis RA were randomized to receive MTX monotherapy or combination therapy (MTX + etanercept or MTX + sulfasalazine + hydroxychloroquine). Participants randomized to receive MTX monotherapy stepped up to combination therapy at 24 weeks if the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) was ≥ 3.2. Results Attrition at 24 weeks was similar in the MTX monotherapy and combination groups. Of the 370 evaluable participants in the initial MTX group, 28% achieved low levels of disease activity and did not step-up to combination therapy (MTX monotherapy group). The mean ± SD DAS28-ESR in participants continuing to take MTX monotherapy at week 102 was 2.7 ± 1.2, which is similar to that in participants who were randomized to immediate combination therapy (2.9 ± 1.2). Participants who received MTX monotherapy had less radiographic progression at week 102 as compared to those who received immediate combination therapy (mean ± SD change in modified Sharp score 0.2 ± 1.1 versus 1.1 ± 6.4. Participants assigned to initial MTX who required step-up to combination therapy at 24 weeks (72%) demonstrated similar DAS28-ESR values (3.5 ± 1.3 vs 3.2 ± 1.3 at week 48) and radiographic progression (change in modified Sharp score 1.2 ± 4.1 vs 1.1 ± 6.4 at week 102) as those assigned to immediate combination therapy. The results for either of the immediate combination approaches, whether triple therapy or MTX + etanercept, were similar. Conclusion These
Haugeberg, Glenn; Bøyesen, Pernille; Helgetveit, Knut; Prøven, Anne
To study short-term and longterm clinical and radiographic outcomes in patients with early rheumatoid arthritis (RA) in the first decade of the biologic treatment era. Patients with early RA diagnosed at a rheumatology outpatient clinic were consecutively enrolled between 1999 and 2001. Data were collected on demographic characteristics, disease activity, patient-reported outcomes, and treatments. Radiographs of hands and feet were performed at baseline and after 2, 5, and 10 years and scored according to the Sharp/van der Heijde method, yielding a modified total Sharp score (mTSS). Mean baseline age for the 94 included patients (36 men and 58 women) was 50.4 years and symptom duration 12.3 months; 67.8% were rheumatoid factor-positive. The proportion of patients in remission and in low, moderate, and high disease activity status was at baseline 4.3%, 1.1%, 35.1%, and 59.6% and at 10 years 52.1%, 20.5%, 27.4%, and 0.0%, respectively. For the period 0-2 years, 62.8% had used prednisolone, 91.5% synthetic disease-modifying antirheumatic drug (DMARD), and 18.1% biologic DMARD, and for the period 2-10 years the numbers were 50.6%, 89.3%, and 62.7%, respectively. At baseline, 70% of the patients had erosions on radiographs. Mean annual change in mTSS was for 0-2 years 3.4, 2-5 years 1.7, and 5-10 years 1.2. A large proportion of our patients with RA diagnosed and treated in the new biologic treatment era achieved a status of clinical remission or low disease activity and had only a minor increase in radiographic joint damage after the first years of followup.
Meyer, Olivier; Nicaise-Roland, Pascale; Santos, Marie dos; Labarre, Colette; Dougados, Maxime; Goupille, Philippe; Cantagrel, Alain; Sibilia, Jean; Combe, Bernard
The objective of this study was to evaluate the potential of serially determined anti-cyclic citrullinated peptide (CCP) antibodies for predicting structural joint damage in patients with early rheumatoid arthritis (RA), compared to a single baseline determination. Ninety-nine RA patients with disease durations of less than one year and no history of disease-modifying antirheumatic drug therapy were followed prospectively for at least five years. Anti-CCP2 concentrations were measured using a second-generation ELISA. Sharp scores as modified by van der Heijde were determined on hand and foot radiographs. Anti-CCP2 antibodies were detected in 55.5% of patients at baseline and 63.6% at any time during the first three years. Presence of anti-CCP2 at any time during the first three years was associated with radiographic damage at baseline (odds ratio (OR), 3.66; 95% confidence interval (95% CI) 0.99–13.54) and with five year progression of the total Sharp score (OR, 3.17; 95% CI, 1.3–7.7), erosion score (OR, 5.3; 95% CI, 1.4–19.2) and joint space narrowing score (OR, 2.8; 95% CI, 1.15–6.8). The presence of anti-CCP2 or IgM RF at baseline did not predict these outcomes. Patients with negative anti-CCP2 tests throughout follow-up had less radiographic progression than patients with increasing anti-CCP2 concentrations; they did not differ from patients with decreasing anti-CCP2 antibody levels. HLADRB1* typing showed that progression of the mean modified Sharp score was not correlated with the presence of the shared epitope alleles. In conclusion, serially determined anti-CCP2 antibodies during the first three years of follow-up performs better than baseline determination for predicting radiographic progression in patients with early RA. PMID:16469118
Fatma, Erdem; Bunyamin, Koc; Savas, Sarikaya; Mehmet, Ucar; Selma, Yazıcı; Ismail, Boyraz; Sabri, Caglar; Gulzade, Ozyalvacli; Ibrahim, Donmez; Mehmet, Yazici
Epidemiologic data indicates that rheumatoid arthritis is an independent risk factor for cardiovascular disease. Epicardial adipose tissue is a novel cardio-metabolic risk factor. Our aim was to evaluate epicardial fat thickness (EFT) using echocardiography in patients with rheumatoid arthritis compared to healthy control subjects. Secondly, we investigated relationship between epicardial fat thickness and clinical and echocardiographic parameters in patients with rheumatoid arthritis. The study population included 76 consecutive patients with rheumatoid arthritis (64 female; mean age, 53 ±11 years, median disease duration, 7.8 years) and 50 healthy subjects as controls (39 female; mean age, 52 ± 6 years). All patients underwent echocardiography to assess left ventricular diastolic dysfunction, left ventricular hypertrophy and EFT. All values were compared between groups. EFT was higher in rheumatoid arthritis patients than in healthy controls (0.66±0.20 vs. 0.54±0.18; p= 0.003). Thickness of Intra Ventricular Septum (IVS) (1.1±0.06 and 9.8±0.08; p=0.001) and posterior wall (PW) (0.98±0.05 and 0.93±0.08; p=0.015) was higher in patients with rheumatoid arthritis compared to healthy controls. Early diastolic myocardiac peak velocity or late diastolic mitral peak velocity (E/A) ratio was lower in rheumatoid arthritis patients compared to healthy patients (1.1 ±0.8 and 1.24±0.1 p=0.001) as well as, E/e' was higher in Rheumatoid arthritis (RA) patients than healthy patients. (E/e':8.7±1.6 and 8.0±1.4 p=0.020). In patients with rheumatoid arthritis, EFT was positively correlated with hypertension and duration of disease and E/e' (r: 0.10, p: 0.010, r: 0.306, p: 0.004 and r: 0.465 p: 0.007 respectively) and EFT was negatively correlated with E/A (r: -.262 p:0.022). To our knowledge, this is the first report about epicardial adipose tissue in rheumatoid arthritis patients. Epicardial fat thickness as an indicator of cardiovascular involvement was higher in
Mc Ardle, Angela; Flatley, Brian; Pennington, Stephen R; FitzGerald, Oliver
Joint destruction, as evidenced by radiographic findings, is a significant problem for patients suffering from rheumatoid arthritis and psoriatic arthritis. Inherently irreversible and frequently progressive, the process of joint damage begins at and even before the clinical onset of disease. However, rheumatoid and psoriatic arthropathies are heterogeneous in nature and not all patients progress to joint damage. It is therefore important to identify patients susceptible to joint destruction in order to initiate more aggressive treatment as soon as possible and thereby potentially prevent irreversible joint damage. At the same time, the high cost and potential side effects associated with aggressive treatment mean it is also important not to over treat patients and especially those who, even if left untreated, would not progress to joint destruction. It is therefore clear that a protein biomarker signature that could predict joint damage at an early stage would support more informed clinical decisions on the most appropriate treatment regimens for individual patients. Although many candidate biomarkers for rheumatoid and psoriatic arthritis have been reported in the literature, relatively few have reached clinical use and as a consequence the number of prognostic biomarkers used in rheumatology has remained relatively static for several years. It has become evident that a significant challenge in the transition of biomarker candidates to clinical diagnostic assays lies in the development of suitably robust biomarker assays, especially multiplexed assays, and their clinical validation in appropriate patient sample cohorts. Recent developments in mass spectrometry-based targeted quantitative protein measurements have transformed our ability to rapidly develop multiplexed protein biomarker assays. These advances are likely to have a significant impact on the validation of biomarkers in the future. In this review, we have comprehensively compiled a list of candidate
Ahmadzadeh, A; Daraei, M; Jalessi, M; Peyvandi, A A; Amini, E; Ranjbar, L A; Daneshi, A
Rheumatoid arthritis is thought to induce conductive hearing loss and/or sensorineural hearing loss. This study evaluated the function of the middle ear and cochlea, and the related factors. Pure tone audiometry, speech reception thresholds, speech discrimination scores, tympanometry, acoustic reflexes, and distortion product otoacoustic emissions were assessed in rheumatoid arthritis patients and healthy volunteers. Pure tone audiometry results revealed a higher bone conduction threshold in the rheumatoid arthritis group, but there was no significant difference when evaluated according to the sensorineural hearing loss definition. Distortion product otoacoustic emissions related prevalence of conductive or mixed hearing loss, tympanometry values, acoustic reflexes, and speech discrimination scores were not significantly different between the two groups. Sensorineural hearing loss was significantly more prevalent in patients who used azathioprine, cyclosporine and etanercept. Higher bone conduction thresholds in some frequencies were detected in rheumatoid arthritis patients that were not clinically significant. Sensorineural hearing loss is significantly more prevalent in refractory rheumatoid arthritis patients.
Garnero, Patrick; Landewé, Robert; Boers, Maarten; Verhoeven, Arco; Van Der Linden, Sjef; Christgau, Stephan; Van Der Heijde, Désirée; Boonen, Annelies; Geusens, Piet
The known risk factors for radiologic progression in rheumatoid arthritis (RA) are not optimally discriminative in patients with early disease who do not have evidence of radiologic damage. We sought to determine whether urinary C-terminal crosslinking telopeptide of type I (CTX-I) and type II (CTX-II) collagen (markers of bone and cartilage destruction, respectively) are associated with long-term radiologic progression in patients with early RA. This was a prospective study of 110 patients with early RA who were participating in the COBRA (Combinatietherapie Bij Reumatoïde Artritis) clinical trial and followup study, a randomized controlled trial comparing the efficacy of oral pulse prednisolone, methotrexate, plus sulfasalazine with sulfasalazine alone. We investigated the relationship between baseline levels of urinary CTX-I and CTX-II and the mean annual progression of joint destruction over a median of 4 years, as measured by changes in the modified Sharp score (average of 2 independent readers). In multivariate logistic regression analysis, baseline urinary CTX-I and CTX-II levels in the highest tertile were the strongest predictors of radiologic progression (Sharp score increase >2 units/year; odds ratio 7.9 and 11.2, respectively), independently of treatment group, erythrocyte sedimentation rate (ESR), Disease Activity Score in 28 joints, rheumatoid factor (RF), and baseline joint damage (Sharp score). The likelihood ratios for a positive test were 3.8 and 8.0 for CTX-I and CTX-II, respectively, which compared favorably with the likelihood ratios for the ESR (3.0), baseline joint damage (1.6), and RF (1.8). When patients were grouped according to the presence (Sharp score >/=4, n = 49) and absence (Sharp score <4, n = 61) of joint damage at baseline, CTX-I and CTX-II levels were predictive only in those without baseline joint damage (odds ratio 14.9 and 25.7, respectively). High baseline levels of urinary CTX-I and CTX-II independently predict an increased
Scott, David L
Some research evidence supports early aggressive treatment of rheumatoid arthritis (RA) using combination therapy with two or more disease modifying anti-rheumatic drugs (DMARDs) plus steroids, or even DMARDs plus an anti-TNF. By contrast, conservatively delayed DMARD monotherapy, given after non-steroidal anti-inflammatory drugs have failed, has been criticised. However, recent long-term studies highlight the complexities in evaluating whether to abandon pyramidal treatment in favour of early DMARDs. Although patients given early DMARD therapy show short-term benefits, longer-term results show no prolonged clinical advantages from early DMARDs. By 5 years patients receiving early DMARDs had similar disease activity and comparable health assessment questionnaire scores to patients who received DMARDs later in their disease course. X-ray progression was persistent and virtually identical in both groups. These negative findings do not invalidate the case for early DMARD therapy, as it is gives sustained reductions in disease activity in the early years of treatment without excessive risks from adverse effects. However, early DMARDs alone do not adequately control RA in the longer term. This may require starting with very aggressive therapy or treating patients more aggressively after early DMARD therapy has been initiated. PMID:14979927
Maijer, Karen I; Gudmann, Natasja Stæhr; Karsdal, Morten Asser; Gerlag, Daniëlle M; Tak, Paul Peter; Bay-Jensen, Anne Christine
Tissue destruction in rheumatoid arthritis (RA) is predominantly mediated by matrix metalloproteinases (MMPs), thereby generating protein fragments. Previous studies have revealed that these fragments include MMP-mediated collagen type I, II, and III degradation, citrullinated and MMP-degraded vimentin and MMP degraded C-reactive protein. We evaluated if biomarkers measuring serum levels of specific sequences of the mentioned fragments would provide further information of diagnostic and/or prognostic processes in early arthritis. Ninety-two early arthritis patients (arthritis duration<1 year, DMARD naïve) were enrolled. Patients either fulfilled the ACR/EULAR2010 criteria for RA (n = 60) or had unclassified arthritis (UA) (n = 32). Patients fulfilling the RA criteria after 2 years follow-up were classified into non-erosive (n = 25), or erosive disease (n = 13). Concentrations of the biomarkers: C1M, C2M, C3M, VICM and CRPM were measured in baseline serum. C1M, C3M and CRPM were able to discriminate between the UA and RA baseline diagnosis in 92 patients with an AUROC of 0.64 (95%CI 0.517 to 0.762), 0.73 (95%CI 0.622 to 0.838) and 0.68 (95%CI 0.570 to 0.795). C2M showed a potential for discrimination between non-erosive and erosive disease in 38 patients with an AUROC of 0.75 (95%CI 0.597 to 0.910). All of the applied biomarkers correlated with one or more of the disease activity parameters: DAS28, ESR, CRP, SJC66, TJC68 and/or HAQ. This is the first study evaluating the applied biomarkers at this early stage of arthritis. C1M, C3M, CRPM might be the best diagnostic marker, whereas high levels of C2M indicated progression of disease at follow-up in early RA patients.
Luz, Karine R; Pinheiro, Marcelo M; Petterle, Giovanna S; Dos Santos, Marla F; Fernandes, Artur R C; Natour, Jamil; Furtado, Rita N V
To propose a novel ultrasound scoring system for hand and wrist joints (US10) for evaluation of patients with early rheumatoid arthritis (RA) and to correlate the US10 with clinical, laboratory and functional variables. Forty-eight early RA patients underwent clinical and laboratory evaluations as well as blinded ultrasound (US) examinations at baseline, three, six and 12 months. The proposed US10 system involved the assessment of the wrist, second and third metacarpophalangeal and proximal interphalangeal joints. The score consisted of inflammation parameters (synovial proliferation [SP], power Doppler [PD] and tenosynovitis [TN]) and joint damage parameters (bone erosion [BE] and cartilage damage [CD]). SP, PD, BE and CD were scored qualitatively (0-1) and semi-quantitatively (grades 0-3). Tenosynovitis was scored as presence/absence. The evaluation also involved the 28-Joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) and C-reactive protein level (CRP). Mean duration of symptoms was 7.58±3.59 months. Significant correlations (p<0.05) were found between inflammation parameters and CRP at baseline and between the changes in these variables throughout the study. Significant correlations (p<0.05) were found between DAS28 score and both PD and TN at baseline and between the changes in DAS28 score and both SP and TN throughout the follow up. Moreover, significant correlations were found between the changes in inflammation parameter scores and HAQ score throughout the follow up. The proposed US10 scoring system proved to be a useful tool for monitoring inflammation and joint damage in early RA patients, demonstrating significant correlations with longitudinal changes in disease activity and functional status. Copyright © 2016. Published by Elsevier Editora Ltda.
Jastifer, James R; Green, Adam
Rheumatoid arthritis is a chronic disease affecting multiple joints of the body. More than 90% of patients affected by rheumatoid arthritis develop foot or ankle pain over the course of their disease. The purpose of the current study was to report ankle dorsiflexion in rheumatoid arthritis patients as well as a control group utilizing a validated measurement instrument. Using a previously validated device, 70 patients presenting with rheumatoid arthritis and 70 controls were measured for ankle range motion and isolated gastrocnemius contractures. Clinical and goniometer measurement of ankle range of motion was also performed. The rheumatoid arthritis group had a mean dorsiflexion of 12.3 degrees compared to a mean of 17.3 degrees in the control group ( P < .05). The difference in dorsiflexion was significantly less utilizing a goniometer than using the validated device, which may be due to measurement technique and external landmarks ( P < .05). Patients with rheumatoid arthritis had less ankle dorsiflexion than the control group. The clinical significance of this study is that it provides evidence that patients with rheumatoid arthritis have decreased ankle dorsiflexion even despite a lack of foot and ankle pain. In light of the high lifetime incidence of foot and ankle pain in these patients, this study provides some evidence that the decreased ankle dorsiflexion may be a contributing factor in foot and ankle pain, but further studies are needed. Level II, prospective cohort study.
Bono, Andrea E; Learreta, Jorge Alfonso; Rodriguez, Graciela; Marcos, Juan Carlos
Temporomandibular joint (TMJ) and stomatognathic system involvement are usually observed during the course of rheumatoid arthritis. This article presents the findings during examination of 190 TMJs from rheumatoid arthritis (RA) patients, and 44 TMJs from controls without RA, including a description of signs and symptoms related to the stomatognathic system, radiological findings in hands-, and TMJ, erythrocyte sedimentation rate (ESR) values, and scores obtained in the Disease Activity Score (Das 28) and the Health Assessment Questionnaire (HAQ). The sample included 57.89% TMJs associated with spontaneous pain, 87.89% with signs of destruction in radiological images, and 58.94% with 20 teeth or less. Restricted mouth opening was detected in 42.1% of RA patients, from which 71% had blocked opening; headache was present in 58%, and pain in the masticatory muscles was found in 57%. TMJ erosions had a significant association with Larsen scores (r=0.62), but not with the Das 28, HAQ, and ESR values. The early evaluation of this joint and the collaborative work of odontologists and rheumatologists are both necessary for a better management of TMJ pathologies.
Hafström, Ingiäld; Engvall, Inga-Lill; Rönnelid, Johan; Boonen, Annelies; van der Heijde, Désirée; Svensson, Björn
Objective To analyse if predictors of radiographic progression differ between patients treated with or without prednisolone in early rheumatoid arthritis (RA). Radiographs of hands and feet were assessed using the modified Sharp/van der Heijde score and radiographic progression was defined as an increase in the total Sharp score above 5.8 (the smallest detectable change). Design Prospective, randomised study of patients with early RA. Setting Secondary level of care; six participating centres from southern Sweden; both urban and rural populations. Participants In all, 225 patients, 64% women, with a diagnosis of RA according to the American College of Rheumatology criteria, were included if they were between 18 and 80 years of age and had a disease duration of less than 1 year. Intervention The patients were randomised to 7.5 mg prednisolone daily for 2 years (P-group; n=108) or no prednisolone (NoP-group; n=117) when they started with their first disease-modifying anti-rheumatic drug and were prospectively followed for 2 years. Results The frequency of patients with radiographic progression after 2 years was 26% in the P-group and 39% in the NoP-group (p=0.033). Relevant interactions between treatment and rheumatoid factor (RF) (p=0.061) and between treatment and anti-cyclic citrullinated peptide 2 (anti-CCP) (p=0.096) were found. RF and anti-CCP independently predicted radiographic progression only in the NoP-group, OR (95% CI) 9.4 (2.5 to 35.2), p=0.001 and OR (95% CI) 8.7 (2.5 to 31.3), p=0.001, respectively. Conclusions The presence of RF and anti-CCP predicted radiographic progression in patients not treated with prednisolone but failed to predict progression in patients treated with this drug. The data suggest that early treatment with prednisolone may modulate not only inflammation but also autoimmunity-associated pathogenetic mechanisms. Trial registration number ISRCTN20612367. PMID:25079933
Zabotti, Alen; Salvin, Sara; Quartuccio, Luca; De Vita, Salvatore
To determine whether ultrasonographic findings of the synovio-entheseal complex of the hand small joints could be used to differentiate between early rheumatoid and early psoriatic arthritis. Thirty-four early rheumatoid and 26 early psoriatic arthritis patients with a prevalent involvement of the hands were examined with ultrasound (US). All exams were performed at the first visit by evaluating synovitis, peritendon extensor digitorum tendon oedema, enthesitis of the central slip of extensor tendon, flexor tenosynovitis and soft tissue oedema. In the same patient, the two most clinically involved joints, if possible of the same digit, were evaluated. Sixty-eight clinically involved joints were evaluated in 34 early rheumatoid arthritis patients and 52 joints in 26 early psoriatic arthritis patients.Synovitis was significantly more frequently detected in early rheumatoid arthritis compared to early psoriatic arthritis patients (p=0.0001), in 91.1% joints of the former and in 59.6% joints of the latter. At metacarpohalangeal joint, the presence of peritendon extensor digitorum tendon inflammation was observed in 2.5% of the joints in the early rheumatoid arthritis group and in 54.1% of the joints in the early psoriatic arthritis group (p=0.0001). At PIP joints, central slip enthesitis was exclusively observed in EPsA (p=0.0045). When considering the most clinically involved finger per patient, soft tissue oedema was detected almost exclusively in psoriatic arthritis (p=0.0002). The US involvement of synovio-entheseal complex and US extrasynovial features may be helpful in the differential diagnosis between early rheumatoid and early psoriatic arthritis.
Performance of matrices developed to identify patients with early rheumatoid arthritis with rapid radiographic progression despite methotrexate therapy: an external validation study based on the ESPOIR cohort data
Granger, Benjamin; Combe, Bernard; Le Loet, Xavier; Saraux, Alain; Guillemin, Francis; Fautrel, Bruno
Introduction Use of prediction matrices of risk or rapid radiographic progression (RRP) for early rheumatoid arthritis (RA) in clinical practice could help to better rationalise the first line of treatment. Before use, they must be validated in populations that have not participated in their construction. The main objective is to use the ESPOIR cohort to validate the performance of 3 matrices (ASPIRE, BEST and SONORA) to predict patients at high risk of RRP at 1 year of disease despite initial treatment with methotrexate (MTX). Methods We selected from the ESPOIR cohort 370 patients receiving MTX or leflunomide (LEF) for ≥3 months within the first year of follow-up. Patients were assessed clinically every 6 months, and structural damage progression seen on radiography was measured by the van der Heijde-modified Sharp score (vSHS) at 1 year. RRP was defined as an increase in the vSHS≥5 points during the first year. Results At 1 year, the mean vSHS score was 1.7±5.0 and 46 patients had RRP. The ASPIRE matrix had only moderate validity in the ESPOIR population, with area under the receiver operating characteristic curve (AUC) <0.7. The AUC for the BEST and SONORA matrices were 0.73 and 0.76. Presence of rheumatoid factor (RF)—or anti-citrullinated protein antibodies (ACPAs) and initial structural damage were always predictive of RRP at 1 year. Disease Activity Score in 28 joints (DAS28) and C reactive protein (ASPIRE threshold) were not associated with RRP. Conclusions Matrices to identify patients at risk of RRP tested in the ESPOIR cohort seem to perform moderately. There is no matrix that shows clearly superior performance. PMID:27252898
Ahmed, Usman; Anwar, Attia; Savage, Richard S.; Costa, Matthew L.; Mackay, Nicola; Filer, Andrew; Raza, Karim; Watts, Richard A.; Winyard, Paul G.; Tarr, Joanna; Haigh, Richard C.; Thornalley, Paul J.; Rabbani, Naila
There is currently no biochemical test for detection of early-stage osteoarthritis (eOA). Tests for early-stage rheumatoid arthritis (eRA) such as rheumatoid factor (RF) and anti–cyclic citrullinated peptide (CCP) antibodies require refinement to improve clinical utility. We developed robust mass spectrometric methods to quantify citrullinated protein (CP) and free hydroxyproline in body fluids. We detected CP in the plasma of healthy subjects and surprisingly found that CP was increased in both patients with eOA and eRA whereas anti–CCP antibodies were predominantly present in eRA. A 4-class diagnostic algorithm combining plasma/serum CP, anti-CCP antibody and hydroxyproline applied to a cohort gave specific and sensitive detection and discrimination of eOA, eRA, other non-RA inflammatory joint diseases and good skeletal health. This provides a first-in-class plasma/serum-based biochemical assay for diagnosis and type discrimination of early-stage arthritis to facilitate improved treatment and patient outcomes, exploiting citrullinated protein and related differential autoimmunity. PMID:25788417
Ahmed, Usman; Anwar, Attia; Savage, Richard S; Costa, Matthew L; Mackay, Nicola; Filer, Andrew; Raza, Karim; Watts, Richard A; Winyard, Paul G; Tarr, Joanna; Haigh, Richard C; Thornalley, Paul J; Rabbani, Naila
There is currently no biochemical test for detection of early-stage osteoarthritis (eOA). Tests for early-stage rheumatoid arthritis (eRA) such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibodies require refinement to improve clinical utility. We developed robust mass spectrometric methods to quantify citrullinated protein (CP) and free hydroxyproline in body fluids. We detected CP in the plasma of healthy subjects and surprisingly found that CP was increased in both patients with eOA and eRA whereas anti-CCP antibodies were predominantly present in eRA. A 4-class diagnostic algorithm combining plasma/serum CP, anti-CCP antibody and hydroxyproline applied to a cohort gave specific and sensitive detection and discrimination of eOA, eRA, other non-RA inflammatory joint diseases and good skeletal health. This provides a first-in-class plasma/serum-based biochemical assay for diagnosis and type discrimination of early-stage arthritis to facilitate improved treatment and patient outcomes, exploiting citrullinated protein and related differential autoimmunity.
Mullan, Ronan H; Matthews, Clare; Bresnihan, Barry; FitzGerald, Oliver; King, Lindsay; Poole, A Robin; Fearon, Ursula; Veale, Douglas J
To investigate whether short-term changes in serum biomarkers of type II collagen degradation (C2C) and types I and II collagen degradation (C1,2C), as well as the biomarker for the synthesis of type II procollagen (CPII) can predict radiographic progression at 1 year following initiation of biologic therapy in patients with inflammatory arthritis. Serum levels of biomarkers were measured at baseline and at 1, 3, 6, 9, and 12 months after initiation of biologic therapy. A composite score reflecting changes from baseline in all 3 biomarkers (DeltaCOL) was calculated. Associations with clinical responses according to the 28-joint count Disease Activity Score and with radiographic progression according to the modified Sharp/van der Heijde score (SHS) were assessed. The 1-year increase in the SHS correlated with the 1-month change in C2C results (r = 0.311, P = 0.028) and the DeltaCOL score (r = 0.342, P = 0.015). Radiographic progression was predicted by increases in serum C2C at 1 month (P = 0.031). The DeltaCOL score was significantly associated with 1-year radiographic progression after 1 (P = 0.022), 3 (P = 0.015), 6 (P = 0.048), and 9 (P = 0.019) months of therapy. Clinical remission was predicted by 1-month decreases in serum levels of C2C (P = 0.008) and C1,2C (P = 0.036). By regression analysis, 1-month changes in C2C, C1,2C, and CPII levels were independently associated with, and correctly predicted radiographic outcome in, 88% of the patients. Short-term changes in serum levels of collagen biomarkers following initiation of biologic therapy may better predict long-term clinical and radiographic outcomes. These collagen biomarkers may therefore be valuable new early indicators of short-term biologic treatment efficacy in clinical trials and in individual patients with inflammatory erosive arthritis.
Crout, J E; Brewer, N S; Tompkins, R B
A review of the clinical features of seven patients with sporotrichosis arthritis showed that six had joint infection without previous skin or lung involvement and that one with myelofibrosis had joint and skin infection. The average time from onset of joint symptoms to diagnosis was 25 months, resulting in joint damage that required arthrodesis in four patients. Tissue from open synovial biopsy was superior to synovial fluid for obtaining a positive culture; concomitant synovial fluid and synovial tissue cultures were superior to either one alone. Granulomatous inflammation was seen in synovial tissue in six patients biopsied. Amphotericin B with surgical debridement of the affected joint was successful treatment in four patients. Although an uncommon cause of joint disease, sporotrichosis arthritis may go unrecognized and mimic other forms of arthritis, resulting in irreparable damage in an otherwise curable form of arthritis.
D'Agostino, Maria-Antonietta; Wakefield, Richard J; Berner-Hammer, Hilde; Vittecoq, Olivier; Filippou, Georgios; Balint, Peter; Möller, Ingrid; Iagnocco, Annamaria; Naredo, Esperanza; Østergaard, Mikkel; Boers, Maarten; Gaillez, Corine; Van Holder, Karina; Le Bars, Manuela
Objectives To study the responsiveness of a combined power Doppler and greyscale ultrasound (PDUS) score for assessing synovitis in biologic-naïve patients with rheumatoid arthritis (RA) starting abatacept plus methotrexate (MTX). Methods In this open-label, multicentre, single-arm study, patients with RA (MTX inadequate responders) received intravenous abatacept (∼10 mg/kg) plus MTX for 24 weeks. A composite PDUS synovitis score, developed by the Outcome Measures in Rheumatology–European League Against Rheumatism (OMERACT–EULAR)-Ultrasound Task Force, was used to evaluate individual joints. The maximal score of each joint was added into a Global OMERACT–EULAR Synovitis Score (GLOESS) for bilateral metacarpophalangeal joints (MCPs) 2–5 (primary objective). The value of GLOESS containing other joint sets was explored, along with clinical efficacy. Results Eighty-nine patients completed the 24-week treatment period. The earliest PDUS sign of improvement in synovitis was at week 1 (mean change in GLOESS (MCPs 2–5): −0.7 (95% CIs −1.2 to −0.1)), with continuous improvement to week 24. Early improvement was observed in the component scores (power Doppler signal at week 1, synovial hyperplasia at week 2, joint effusion at week 4). Comparable changes were observed for 22 paired joints and minimal joint subsets. Mean Disease Activity Score 28 (C reactive protein) was significantly reduced from weeks 1 to 24, reaching clinical meaningful improvement (change ≥1.2) at week 8. Conclusions In this first international prospective study, the composite PDUS score is responsive to abatacept. GLOESS demonstrated the rapid onset of action of abatacept, regardless of the number of joints examined. Ultrasound is an objective tool to monitor patients with RA under treatment. Trial registration number NCT00767325. PMID:26590174
Barlow, Jonathan D.; Abboud, Joseph
Young patients with glenohumeral arthritis are an ongoing treatment challenge. They typically have high demands of their shoulders, require long-term durability due to their young age, and often have altered local anatomy, through their disease process (instability arthropathy, juvenile rheumatoid arthritis, etc.) or from previous surgery (capsulorraphy arthropathy, chondrolysis, etc.). Workup to evaluate underlying causes of early arthritis, and to exclude infectious causes are necessary. When nonoperative management fails, arthroscopic debridement, hemiarthroplasty (isolated, with glenoid reaming, or with biological interposition), and total shoulder arthroplasty are treatment options available to the treating surgeon. Debridement or hemiarthroplasty can provide pain relief for a subset of patients, but results have not been reproducible across the literature and have not been durable over time. Total shoulder arthroplasty provides the most reliable pain relief, but long-term glenoid loosening and wear continue to lead to high revision rates in this patient population. PMID:26980987
Werner, David; Simon, David; Englbrecht, Matthias; Stemmler, Fabian; Simon, Christoph; Berlin, Andreas; Haschka, Judith; Renner, Nina; Buder, Thomas; Engelke, Klaus; Hueber, Axel J; Rech, Jürgen; Schett, Georg; Kleyer, Arnd
To characterize the specific structural properties of the erosion-prone bare area of the human joint, and to search for early microstructural changes in this region during rheumatoid arthritis (RA). In the initial part of the study, human cadaveric hand joints were examined for exact localization of the bare area of the metacarpal heads, followed by detection of cortical micro-channels (CoMiCs) in this region by high-resolution peripheral quantitative computed tomography (HR-pQCT) and, after anatomic dissection, validation of the presence of CoMiCs by micro-computed tomography (micro-CT). In the second part of the study, the number and distribution of CoMiCs were analyzed in 107 RA patients compared to 105 healthy individuals of similar age and sex distribution. Investigation by HR-pQCT combined with adaptive thresholding allowed the detection of CoMiCs in the bare area of human cadaveric joints. The existence of CoMiCs in the bare area was additionally validated by micro-CT. In healthy individuals, the number of CoMiCs increased with age. RA patients showed significantly more CoMiCs compared to healthy individuals (mean ± SD 112.9 ± 54.7/joint versus 75.2 ± 41.9/joint; P < 0.001), with 20-49-year-old RA patients exhibiting similar numbers of CoMiCs as observed in healthy individuals older than age 65 years. Importantly, CoMiCs were already found in RA patients very early in their disease course, with enrichment in the erosion-prone radial side of the joint. CoMiCs represent a new form of structural change in the joints of patients with RA. Although the number of CoMiCs increases with age, RA patients develop CoMiCs much earlier in life, and such changes can even occur at the onset of the disease. CoMiCs therefore represent an interesting new opportunity to assess structural changes in RA. © 2017, American College of Rheumatology.
Errichetti, Enzo; Zabotti, Alen; Stinco, Giuseppe; Quartuccio, Luca; Sacco, Stefania; De Marchi, Ginevra; Piccirillo, Angelo; De Vita, Salvatore
Differentiation between psoriatic arthritis (PsA) sine psoriasis and rheumatoid arthritis (RA) may be a challenge, especially in the early stages, hence the need for new instrumental markers to assist their diagnosis. In this study, we investigated possible dermoscopic differences in vascular appearance of nail fold and elbow (a classic site of repeated trauma) in these two conditions. Fifteen patients with PsA sine psoriasis, 12 patients with RA and 12 controls were included in the study. Regarding the nail fold vascular appearance in PsA sine psoriasis and RA cohorts, the presence of diffuse reddish background with or without sparse dotted vessels was significant in the former, whereas the evidence of parallel dotted/short linear vessels ("fish school-like" pattern) or irregular/ramified, blurry, purple vessels were significant in the latter; none of these patterns were detected in the control group. Regarding the elbow, the pattern significantly associated with PsA sine psoriasis consisted of diffusely distributed, red, dotted vessels. On the other hand, RA patients and controls displayed similar dermoscopic findings, with three possible vascular patterns being observed: (i) irregular, blurry, purple vessels; (ii) avascular appearance; and (iii) sparse, dotted, purple vessels. In conclusion, dermoscopy may be a useful supportive tool for differentiating early PsA sine psoriasis from RA. © 2016 Japanese Dermatological Association.
Vojinovic, Jelena; Tincani, Angela; Sulli, Alberto; Soldano, Stefano; Andreoli, Laura; Dall'Ara, Francesca; Ionescu, Ruxandra; Pasalic, Katarina Simic; Balcune, Inete; Ferraz-Amaro, Ivan; Tlustochowicz, Małgorzata; Butrimiene, Irena; Punceviciene, Egle; Toroptsova, Natalia; Grazio, Simeon; Morovic-Vergles, Jadranka; Masaryk, Pavol; Otsa, Kati; Bernardes, Miguel; Boyadzhieva, Vladimira; Salaffi, Fausto; Cutolo, Maurizio
To collect data on vitamin D (25(OH)D) serum levels in a large number of rheumatoid arthritis (RA) patients from different European countries, to investigate their relation with disease activity, disability, quality of life, and possibly to construct a new Patient Reported Outcome (PRO) questionnaire in order to self-estimate if they are at risk for vitamin D insufficiency/deficiency-related clinical implications (D-PRO). This was a European League Against Rheumatism (EULAR) supported cross-sectional study (project No CLI064) which involved 625 RA patients (mean age 55±11years, mean disease duration 11±9years), 276 age and sex matched healthy subjects, and rheumatologists working in academic institutions or hospital centres, as well as PARE organizations (patient representatives) from 13 European countries. Serum samples for 25(OH)D level measurement were collected during winter time and analyzed in a central laboratory using chemiluminescence immunoassay (DiaSorin). Patient past medical history was recorded. RA patients were provided with three questionnaires: the Rheumatoid Arthritis Impact Diseases score (RAID), the Health Assessment Questionnaire (HAQ), and the new D-PRO questionnaire at the time of 25(OH)D serum sampling. D-PRO questionnaire consisted of three domains, Symptom Risk Score (SRS), Habitus Risk Score (HRS) and Global Risk Score (SRS+HRS=GRS), constructed with items possibly related to vitamin D deficiency. D-PRO was correlated with both clinical and PRO scores. DAS28-CRP was also evaluated. Statistical analysis was performed by non parametric tests. Mean serum concentration of 25(OH)D in RA patients (17.62±9.76ng/ml) was found significantly lower if compared to the levels obtained in matched controls (18.95±9.45ng/ml) (p=0.01), with statistically significant differences among several European countries. Negative correlations were found between 25(OH)D serum levels and DAS28-CRP (p<0.001), RAID (p=0.05) and HAQ (p=0.04) scores in the RA
Cambridge, Geraldine; Moura, Rita A.; Santos, Tania; Khawaja, Akif A.; Polido-Pereira, Joaquim; Canhão, Helena; Leandro, Maria J.; Fonseca, João E.
Background The pre-symptomatic stage of Rheumatoid arthritis (RA) is associated with pro-inflammatory cytokines and autoantibodies. High levels and epitope spread by Rheumatoid factors (RhF) and autoantibodies to citrullinated proteins signify progression towards disease expression. In established RA, the persistence of high autoantibody levels reflects production by both long-lived plasma cells and short-lived plasmablasts. Neither the relative contributions to pathogenesis by autoantibodies from either source, nor the factors responsible for deciding the fate of autoantigen specific ‘parent’ B-cells, is understood. Phenotypic markers identifying subsets of autoreactive B-cells are therefore of interest in understanding the origin and perpetuation of the autoimmune response in RA. One such phenotypic marker is the rat monoclonal antibody, 9G4, which recognises an idiotope on immunoglobuins derived from the inherently autoreactive VH-gene, VH4-34. We therefore investigated whether the 9G4 idiotope was expressed on autoantibodies in patients with RA. Methodology/Principal Findings Sera from 19 patients with established RA and those with <1year history of untreated polyarthritis either resolving into RA (n = 42) or non-RA diagnosis (n = 31) were included. Autoantibodies to cyclic citrullinated peptides (CCP), RhF and co-expression of the 9G4 idiotope were measured by ELISA. 9G4 recognised a population of anti-CCP antibodies in the majority of sera from patients with established disease and also in samples from patients with early disaese. 9G4+RhF levels were generally lower and not associated with positivity for, or levels of 9G4+CCP. Conclusions/Significance The persistence of 9G4+ immunoglobulins, of any isotype, in serum is rare. We describe here the novel finding of 9G4 expression on anti-CCP antibodies in patients from the earliest symptoms of RA through to established disease. Our results suggest that 9G4 expression on anti-CCP autoantibodies was
Cambridge, Geraldine; Moura, Rita A; Santos, Tania; Khawaja, Akif A; Polido-Pereira, Joaquim; Canhão, Helena; Leandro, Maria J; Fonseca, João E
The pre-symptomatic stage of Rheumatoid arthritis (RA) is associated with pro-inflammatory cytokines and autoantibodies. High levels and epitope spread by Rheumatoid factors (RhF) and autoantibodies to citrullinated proteins signify progression towards disease expression. In established RA, the persistence of high autoantibody levels reflects production by both long-lived plasma cells and short-lived plasmablasts. Neither the relative contributions to pathogenesis by autoantibodies from either source, nor the factors responsible for deciding the fate of autoantigen specific 'parent' B-cells, is understood. Phenotypic markers identifying subsets of autoreactive B-cells are therefore of interest in understanding the origin and perpetuation of the autoimmune response in RA. One such phenotypic marker is the rat monoclonal antibody, 9G4, which recognises an idiotope on immunoglobuins derived from the inherently autoreactive VH-gene, VH4-34. We therefore investigated whether the 9G4 idiotope was expressed on autoantibodies in patients with RA. Sera from 19 patients with established RA and those with <1year history of untreated polyarthritis either resolving into RA (n = 42) or non-RA diagnosis (n = 31) were included. Autoantibodies to cyclic citrullinated peptides (CCP), RhF and co-expression of the 9G4 idiotope were measured by ELISA. 9G4 recognised a population of anti-CCP antibodies in the majority of sera from patients with established disease and also in samples from patients with early disaese. 9G4+RhF levels were generally lower and not associated with positivity for, or levels of 9G4+CCP. The persistence of 9G4+ immunoglobulins, of any isotype, in serum is rare. We describe here the novel finding of 9G4 expression on anti-CCP antibodies in patients from the earliest symptoms of RA through to established disease. Our results suggest that 9G4 expression on anti-CCP autoantibodies was not due to polyclonal expansion of VH4-34-encoded immunoglobulins. These
Duquenne, Carole; Cornec, Divi; Marhadour, Thierry; Jousse-Joulin, Sandrine; Cantagrel, Alain; Pavy, Stephan; Devauchelle-Pensec, Valérie; Saraux, Alain
In patients with early arthritis naive to disease-modifying antirheumatic drugs, we evaluated the prevalence of initial and persistent lymphopenia, underlying diagnoses, and risk of infection or malignancy. Eight hundred and thirteen patients with early arthritis included in the ESPOIR cohort had a clinical examination, laboratory tests (viral serology, immunological tests, and cytokine profile), and radiographs. We determined the prevalence of lymphopenia at baseline and after 3 years, associated factors, diagnoses, and risk of infection or malignancy. At baseline, 50/813 (6.2%) patients had lymphopenia. Lymphopenia was associated with positive rheumatoid factor (P=0.02), cytopenia (P≤0.05), hepatitis C (P=0.05), higher C-reactive protein and DAS28 (P≤0.05 for both). Cytokine profile and radiological progression were not significantly different between patients with and without lymphopenia. Suspected diagnoses at inclusion were rheumatoid arthritis (RA, n=27), unclassified arthritis (n=15), systemic lupus erythematosus (SLE, n=3), spondyloarthritis (n=2), Sjögren's syndrome (n=1), hematologic disease (n=1), and fibromyalgia (n=1). Fifteen patients out of 42 (35.7%) with initial lymphopenia had persistent lymphopenia after 3 years, including 5 with documented causes (lupus, hepatitis C, undernutrition, azathioprine, and tamoxifen); none had PVB19, HIV, or HBV infection and none experienced infections, solid or hematologic malignancies during follow-up. Final diagnoses in these 15 patients were RA (n=6), unclassified arthritis (n=6), SLE (n=1), spondyloarthritis (n=1), and fibromyalgia (n=1). Lymphopenia is rare in early arthritis. The most common rheumatic cause is RA, in which marked inflammation and other cytopenias are common. Lymphopenia in early arthritis is often short-lived, even when methotrexate is prescribed. Copyright © 2015. Published by Elsevier SAS.
Haye Salinas, María Jezabel; Retamozo, Soledad; Alvarez, Ana Cecilia; Maldonado Ficco, Hernán; Dal Pra, Fernando; Citera, Gustavo; Benegas, Mariana; Chaparro del Moral, Rafael; Rillo, Oscar; Secco, Anastasia; Marino Claverie, Lucila; Catalan Pellet, Antonio; Marcos, Josefina; García, Mercedes Argentina; Marcos, Juan Carlos; Barbaglia, Ana; Bellomio, Verónica; Berman, Alberto; Quiroz, Cristian; Soriano, Enrique R; Ceccato, Federico; Paira, Sergio; Vazquez, Doralia; Juarez, Vicente Ricardo; Velozo, Edson Javier; Salvatierra, Gabriela; Caeiro, Francisco
Our objective was to analyze the effects of cigarette smoking on disease activity, functional capacity, radiographic damage, serology and presence of extraarticular manifestations in patients with rheumatoid arthritis and undifferentiated arthritis. This is a cross-sectional study of 1,305 patients (729 with rheumatoid arthritis and 576 with undifferentiated arthritis) from CONAART, the Argentine Consortium for Early Arthritis that includes patients older than 16 years with <2 years of disease. Sociodemographic data, clinical characteristics of the disease and smoking history were collected. In patients with rheumatoid arthritis the disease activity score of 28 joints was 5.4 ± 1.3 in current smokers, 5.2 ± 1.4 in former smokers and 5.1 ± 1.4 in never smokers (p = 0.011). The simple erosion narrowing score was higher in current smokers and former smokers than in never smokers (M 14.0, R Q 6.0-21.0; M 15.0, R Q 7.0-24.0; M 10.0, R Q 5.0-17.0; p = 0.006). Current smokers had higher rheumatoid factor titer (M 160.0, R Q 80.0-341.0) than former smokers (M 146.8, R Q 6.03-255.5) and never smokers (M 15.0, R Q 9.0-80.0) (p = 0.004). The variable independently associated with tobacco exposure was simple erosion narrowing score (OR = 1.03, 95 % CI 1.00-1.05; p = 0.012). In patients with undifferentiated arthritis, an association between smoking status and parameters of activity or radiographic damage was not observed. Neither was tobacco exposure related to the presence of extraarticular manifestations or to the degree of disability in any of the two groups of patients. No relation was found between disease activity and severity, and number of packs smoked per year. Tobacco.
Wong, Lauren E; Huang, Wei-Ti; Pope, Janet E; Haraoui, Boulos; Boire, Gilles; Thorne, J Carter; Hitchon, Carol A; Tin, Diane; Keystone, Edward C; Bykerk, Vivian P
Studies suggest that hormonal states affect disease characteristics in women with rheumatoid arthritis (RA). This study investigated how age at menopause affects disease in women presenting with early RA. This was a cross-sectional study of postmenopausal women with early RA under age 65 years at time of enrollment in the Canadian Early Arthritis Cohort. RA-related disease characteristics in women who had early age at menopause (EM; age at menopause <45 years) were compared to those who had usual age at menopause (age at menopause ≥45 years). The t-test was applied to continuous variables and the chi-square test to categorical variables. Multivariate logistic regression analysis was used to adjust for age at menopause, smoking, and use of exogenous hormones. A total of 534 women were included; 93 were in the EM group. The age at RA onset was similar between groups. The EM group had higher mean patient global and pain scores and was more likely to be rheumatoid factor (RF) positive and meet the 1987 American College of Rheumatology criteria for RA. Using multivariate logistic regression, the EM group was more likely to be RF positive (odds ratio 2.2 [95% confidence interval 1.3-3.8], P = 0.005). Symptom duration, joint counts, Disease Activity Score in 28 joints, Health Assessment Questionnaire scores, and inflammatory markers did not differ between groups. These data suggest that early age at menopause, compared to usual age at menopause, is associated with seropositivity in women with early RA. © 2015, American College of Rheumatology.
Scott, Ian C; Ibrahim, Fowzia; Simpson, Gemma; Kowalczyk, Anna; White-Alao, Beverley; Hassell, Andrew; Plant, Michael; Richards, Selwyn; Walker, David; Scott, David L
The effectiveness of anakinra (interleukin-1 receptor antagonist) in early rheumatoid arthritis (RA) is unknown. We evaluated the efficacy of anakinra (combined with methotrexate) in a randomised clinical trial of early active RA patients. The Combination Anti-Rheumatic Drugs in Early RA-2 (CARDERA-2) trial was a randomised trial of early (duration <1 year) active RA. Patients were randomised to 12 months of: (1) methotrexate or (2) anakinra-methotrexate. Follow-up lasted 2 years. The primary outcome was erosive progression (changes from baseline in modified Larsen scores). Secondary outcomes were changes from baseline in disease activity score on a 28-joint count (DAS28), health assessment questionnaire (HAQ), and quality of life (EQ-5D) scores alongside ACR responder rates. 154 patients received the allocated intervention (from 259 screened). Similar Larsen score progression was seen at 12 and 24 months in patients receiving anakinra-methotrexate (mean changes from baseline of 2.50 and 5.10, respectively) and methotrexate monotherapy (mean changes from baseline of 4.16 and 5.20, respectively). Lower improvements in DAS28 and HAQ scores were seen at all time-points in anakinra-methotrexate treated patients; these were significantly less at 24 months (DAS28 p=0.04; HAQ P=0.02). Significantly lower EQ-5D score increases were seen at 12 months with anakinra-methotrexate (p=0.03). Anakinra-methotrexate was associated with more serious adverse events compared with methotrexate monotherapy (11 vs. 6 patients), although this was not significant (p=0.59). Anakinra (combined with methotrexate) is not effective in early, active RA. It provided no clinical benefits beyond methotrexate monotherapy.
Background The main aim of the study was to investigate the relationship between persistent disease activity and radiographic progression of joint damage in early rheumatoid arthritis (ERA). Methods Forty-eight patients with active ERA was assessed every 3 months for disease activity for 3 years. Radiographic damage was measured by the Sharp/van der Heijde method (SHS). The cumulative inflammatory burden was estimated by the time-integrated values (area under the curve-AUC) of Disease Activity Score 28 joint based on C-reactive protein (DAS28-CRP) in rapid progressors versus non-progressors. Bland and Altman's 95% limits of agreement method were used to estimate the smallest detectable difference (SDD) of radiographic progression. The relationship between clinical and laboratory predictors of radiographic progression and their interactions with time was analysed by logistic regression model. Results After 3-years of follow-up, radiographic progression was observed in 54.2% (95%CI: 39.8% to 67.5%) of patients and SDD was 9.5 for total SHS. The percentage of patients with erosive disease increased from 33.3% at baseline to 76% at 36 months. The total SHS of the progressors worsened from a median (interquartile range) of 18.5 (15-20) at baseline to 38.5 (34-42) after 3 years (p < 0.0001) whereas non-progressors worsened from a median of 14.5 (13-20) at baseline to 22.5 (20-30) after 3 years (p < 0.001). In the regression model, time-integrated values of DAS28-CRP and anti-CCP positivity have the highest positive predictive value for progression (both at level of p < 0.0001). Radiographic progression was also predicted by a positive IgM-RF (p0.0009), and a high baseline joint damage (p = 0.0044). Conclusions These data indicate that the level of disease activity, as measured by time-integrated DAS28-CRP, anti-CCP and IgM-RF positivity and a high baseline joint damage, affects subsequent progression of radiographic damage in ERA. PMID:21624120
Pandya, Jayesh M; Lundell, Anna-Carin; Hallström, Magnus; Andersson, Kerstin; Nordström, Inger; Rudin, Anna
The pathogenic role and frequency of T cell subtypes in early rheumatoid arthritis are still unclear. We therefore performed a comprehensive analysis of the circulating T cell subtype pattern in patients with untreated early rheumatoid arthritis compared to healthy control subjects. Peripheral blood mononuclear cells were obtained from 26 patients with untreated early rheumatoid arthritis and from with 18 age- and sex-matched healthy control subjects. T helper cell types Th0, Th1, Th2, Th17, and Th1/17 and nonclassic T helper subsets were defined by flow cytometry based on the expression of chemokine receptors CCR4, CCR6, and CXCR3. Regulatory T cells were defined by expression of CD25(+) CD127(low) and also FOXP3 CXCR5(+) cells among regulatory and nonregulatory T cells were defined as T follicular regulatory and T follicular helper cells, respectively. The phenotype of T cell subsets was confirmed by transcription factor and cytokine secretion analyses. Multivariate discriminant analysis showed that patients with untreated early rheumatoid arthritis were segregated from healthy control subjects based on the circulating T cell subset profile. Among the discriminator subsets, CCR4(+)CXCR3(-) (Th2 and Th17), CTLA4(+) and FOXP3(+) subsets were present in significantly higher frequencies, whereas CCR4(-) (Th1/Th17, CCR6(+)CCR4(-)CXCR3(-), and Th1) subsets were present in lower frequencies in patients with untreated early rheumatoid arthritis compared with healthy control subjects. The proportions of Th2 and Th17 subsets associated positively with each other and negatively with the CXCR3(+)/interferon γ-secreting subsets (Th1 and Th1/Th17) in patients with untreated rheumatoid arthritis. The proportions of Th2 cells increased with age in patients with untreated early rheumatoid arthritis and healthy control subjects. The dominance of circulating CCR4(+)CXCR3(-) T helper subsets (Th2 and Th17) in untreated early rheumatoid arthritis point toward a pathogenic role of
Zhang, Wei; Bansback, Nick; Sun, Huiying; Pedersen, Ronald; Kotak, Sameer; Anis, Aslam H
Objective To assess changes in work productivity in patients who have achieved response using etanercept (ETN) 50 mg+methotrexate (MTX) (phase I) are randomised to ETN 25 mg+MTX versus MTX versus placebo (phase II) and then withdrawn from treatment (phase III). Methods Patients included in the analysis were in employment entering phase II of the PRIZE trial and had one or more follow-ups. Phase II was a 39-week, randomised and double-blind comparison of the 3 dose-reduction treatments. Phase III was a 26-week observational study where treatment was withdrawn. The Valuation of Lost Productivity was completed approximately every 13 weeks to estimate productivity impacts from a societal perspective. Results A total of 120 participants were included in our analyses. During phase II, ETN25+MTX or MTX improved paid work productivity by over 100 hours compared with placebo, amounting to a gain of €1752 or €1503, respectively. ETN25+MTX compared with placebo gains €1862 in total paid/unpaid productivity. At week 52, the 3-month paid work productivity loss was 21.8, 12.8 and 14.0 hours, respectively. The productivity loss increased at week 64 from week 52, dropped at week 76 for all treatment groups and then continued rising after week 76 for the placebo group (71.9 hours at week 91) but not for the other 2 groups (21.9 hours for ETX25+MTX and 27.6 hours for MTX). Conclusions The work productivity gain in phase I as a result of ETN50+MTX was marginally lost in the dose-reduction treatment groups, ETN25+MTX and MTX, but substantially lost in the placebo group during phase II. Trial registration number NCT00913458; Results. PMID:27486524
Bacconnier, Ludovic; Rincheval, Nathalie; Flipo, René-Marc; Goupille, Philippe; Daures, Jean-Pierre; Boulenger, Jean-Philippe; Combe, Bernard
RA is a chronic disease with frequent psychological co-morbidities, of which depression and anxiety are two common manifestations. We aimed to identify predictive factors of psychological distress in a large prospective cohort of very early RA patients. ESPOIR (Etude et Suivi des Polyarthrites Indifférenciées Récentes) is a multicentre, longitudinal and prospective cohort study of patients with early arthritis (<6 months disease duration). The study sample comprised 641 patients with very early RA according to the 2010 ACR/European League Against Rheumatism RA criteria from the ESPOIR cohort. Psychological distress was assessed over 3 years by the five-item Mental Health Inventory questionnaire at various time points (baseline, 6, 12, 18, 24 and 36 months). Logistic regression with a generalized estimating equation model was used to analyse the association of disease variables and risk of psychological distress. At baseline, 46.9% of RA patients were screened as positive for psychological distress. Over 3 years, psychological distress decreased significantly, with a prevalence of 25.8% at 36 months. The HAQ Disability Index (HAQ-DI) score was the most important factor predicting psychological distress over 3 years [odds ratio 2.10 (95% CI 1.41, 3.14)-3.59 (2.29, 5.63)]. Baseline biological and radiological variables and treatment regimens were not associated with distress. Psychological distress in very early RA is frequent and the HAQ-DI score is a predictor of depression and anxiety in these patients. A psychological evaluation in patients with early RA is important for further individual psychiatric diagnosis and management. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: email@example.com.
The aim of the research was to study biomarkers of osteochondral lesions on early stages of rheumatoid arthritis (RA). The data showed the prognostic value of indicators of the erosive and destructive changes of joints in early and in the advanced stage of RA. Indicators that determine how directly, inflammatory process activity and markers associated with the speed and staging damage of articular surfaces is analyzed. That can adequately justify individualized clinical strategy in patients with early RA.
Boulware, Dennis W.; Byrd, Shannon L.
Exercise can help decrease pain and improve function in people with rheumatoid arthritis or osteoarthritis. Physicians must provide individualized, realistic, enjoyable exercise programs that help affected joints, build fitness, and maximize patient compliance. Physicians must also provide appropriate follow-up care, adjusting the exercise program…
Boulware, Dennis W.; Byrd, Shannon L.
Exercise can help decrease pain and improve function in people with rheumatoid arthritis or osteoarthritis. Physicians must provide individualized, realistic, enjoyable exercise programs that help affected joints, build fitness, and maximize patient compliance. Physicians must also provide appropriate follow-up care, adjusting the exercise program…
Erov, N K
The author describes 2 cases of erroneous prescription of rumalon to patients with rheumatoid arthritis (RA), as a result of which in one of the patients oligoarthritis arthritis while in the other one the typical seropositive slow-progressing rheumatoid arthritis transformed to RA with systemic manifestations.
Haddad, Amir; Zisman, Devy
Epidemiological studies have shown that patients with psoriatic arthritis (PsA) are often affected by numerous comorbidities that carry significant morbidity and mortality. Reported comorbidities include diabetes mellitus, obesity, metabolic syndrome, cardiovascular diseases, osteoporosis, inflammatory bowel disease, autoimmune eye disease, non-alcoholic fatty liver disease, depression, and fibromyalgia. All health care providers for patients with PsA should recognize and monitor those comorbidities, as well as understand their effect on patient management to ensure an optimal clinical outcome. PMID:28178440
Demoruelle, M Kristen; Deane, Kevin D
Data now suggest that current strategies in the treatment of rheumatoid arthritis (RA) should focus on early identification and diagnosis, followed by early initiation of DMARD therapy. Initiation of treatment in early RA-ideally, less than 3-6 months after symptom onset-improves the success of achieving disease remission and reduces joint damage and disability. While the optimal treatment regimen in early RA is unclear, use of initial DMARD mono- or combination therapy with prompt escalation to achieve low disease activity or remission is an appropriate approach. Ultimately, the goal of RA management should be the prevention of inflammatory joint disease and, thereby, prevention of disability. To date, studies have shown that pharmacologic interventions can delay progression from undifferentiated inflammatory arthritis to classifiable RA. However, further investigation is needed to identify asymptomatic individuals at high risk for future RA and to intervene early enough in the pathogenesis of RA to prevent progression to clinical disease.
Demoruelle, M. Kristen
Data now suggest that current strategies in the treatment of rheumatoid arthritis (RA) should focus on early identification and diagnosis, followed by early initiation of DMARD therapy. Initiation of treatment in early RA—ideally, less than 3–6 months after symptom onset—improves the success of achieving disease remission and reduces joint damage and disability. While the optimal treatment regimen in early RA is unclear, use of initial DMARD mono- or combination therapy with prompt escalation to achieve low disease activity or remission is an appropriate approach. Ultimately, the goal of RA management should be the prevention of inflammatory joint disease and, thereby, prevention of disability. To date, studies have shown that pharmacologic interventions can delay progression from undifferentiated inflammatory arthritis to classifiable RA. However, further investigation is needed to identify asymptomatic individuals at high risk for future RA and to intervene early enough in the pathogenesis of RA to prevent progression to clinical disease. PMID:22773387
Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone with elevated levels of proinflammatory cytokines. It has been reported that IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. It remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we tried to identify Th17 cells, Th1 cells, and Th17 cell-derived Th1 cells (CD161(+)Th1 cells) in the peripheral blood of early-onset RA patients. We also evaluated the effect of methotrexate on the ratio of Th17 cells in early-onset RA patients. The ratio of Th17 cell-derived Th1 cells to CD161(+)Th17 cells was elevated in the peripheral blood of early-onset RA patients. In addition, MTX reduced the ratio of Th17 cells but not Th1 cells. These findings suggest that IL-17 and Th17 play important roles in the early phase of RA; thus, anti-IL-17 antibodies should be administered to patients with RA in the early phase.
Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone with elevated levels of proinflammatory cytokines. It has been reported that IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. It remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we tried to identify Th17 cells, Th1 cells, and Th17 cell-derived Th1 cells (CD161+Th1 cells) in the peripheral blood of early-onset RA patients. We also evaluated the effect of methotrexate on the ratio of Th17 cells in early-onset RA patients. The ratio of Th17 cell-derived Th1 cells to CD161+Th17 cells was elevated in the peripheral blood of early-onset RA patients. In addition, MTX reduced the ratio of Th17 cells but not Th1 cells. These findings suggest that IL-17 and Th17 play important roles in the early phase of RA; thus, anti-IL-17 antibodies should be administered to patients with RA in the early phase. PMID:27123445
Raychaudhuri, Siba P; Wilken, Reason; Sukhov, Andrea C; Raychaudhuri, Smriti K; Maverakis, Emanual
Psoriatic arthritis (PsA) is a heterogeneous disease that can involve a variety of distinct anatomical sites including a patient's peripheral and axial joints, entheses, skin and nails. Appropriate management of PsA requires early diagnosis, monitoring of disease activity, and utilization of cutting edge therapies. To accomplish the former there are a variety of PsA-specific tools available to screen, diagnose, and assess patients. This review will outline the recently developed PsA screening tools, including the Toronto Psoriatic Arthritis Screening Questionnaire (TOPAS), the Psoriasis Epidemiology Screening Tool (PEST), the Psoriatic Arthritis Screening and Evaluation (PASE), and the Psoriasis and Arthritis Screening Questionnaire (PASQ). We will also review the Classification Criteria for Psoriatic Arthritis (CASPAR) and current PsA disease severity measures, such as the Disease Activity index for Psoriatic Arthritis (DAPSA), the Psoriatic Arthritis Joint Activity Index (PsAJAI) and the Composite Psoriatic Disease Activity Index (CPDAI). As is the case for PsA screening and assessment tools, there are also a variety of new therapies available for PsA. Historically, patients with PsA were treated with NSAIDS and traditional disease-modifying anti-rheumatic drugs (DMARDs). However, the ability of these medications to slow down the radiographic progression of joint disease has not been demonstrated. In contrast, anti-TNF agents, such as etanercept, infliximab, adalimumab, golimumab and certolizumab, are effective in this regard. Emerging PsA treatments include an oral phosphodiesterase 4 inhibitor, apremilast; a Janus kinase (JAK) inhibitor, tofacitinib; and several new biologics that target the IL-23/IL-17 pathway including secukinumab, brodalumab, ixekizumab, and ustekinumab. Herein we will review the mechanisms of action of these drugs, their results in clinical trials, and guidelines for administration. Lastly, treatment recommendations from the European League
Combe, Bernard; Landewe, Robert; Daien, Claire I; Hua, Charlotte; Aletaha, Daniel; Álvaro-Gracia, Jose María; Bakkers, Margôt; Brodin, Nina; Burmester, Gerd R; Codreanu, Catalin; Conway, Richard; Dougados, Maxime; Emery, Paul; Ferraccioli, Gianfranco; Fonseca, Joao; Raza, Karim; Silva-Fernández, Lucía; Smolen, Josef S; Skingle, Diana; Szekanecz, Zoltan; Kvien, Tore K; van der Helm-van Mil, Annette; van Vollenhoven, Ronald
Since the 2007 recommendations for the management of early arthritis have been presented, considerable research has been published in the field of early arthritis, mandating an update of the 2007 European League Against Rheumatism (EULAR) recommendations for management of early arthritis. In accordance with the 2014 EULAR Standardised Operating Procedures, the expert committee pursued an approach that was based on evidence in the literature and on expert opinion. The committee involved 20 rheumatologists, 2 patients and 1 healthcare professional representing 12 European countries. The group defined the focus of the expert committee and target population, formulated a definition of 'management' and selected the research questions. A systematic literature research (SLR) was performed by two fellows with the help of a skilled librarian. A set of draft recommendations was proposed on the basis of the research questions and the results of the SLR. For each recommendation, the categories of evidence were identified, the strength of recommendations was derived and the level of agreement was determined through a voting process. The updated recommendations comprise 3 overarching principles and 12 recommendations for managing early arthritis. The selected statements involve the recognition of arthritis, referral, diagnosis, prognostication, treatment (information, education, pharmacological and non-pharmacological interventions), monitoring and strategy. Eighteen items were identified as relevant for future research. These recommendations provide rheumatologists, general practitioners, healthcare professionals, patients and other stakeholders with an updated EULAR consensus on the entire management of early arthritis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Erum, Uzma; Ahsan, Tasnim; Khowaja, Danish
Objective: To determine the frequency of dyslipidemia in patients with Rheumatoid Arthritis. Methods: This is a prospective, cross-sectional, observational study, conducted at the ‘Rheumatology Clinic’ of Jinnah Postgraduate Medical Center (JPMC), Karachi, from November 2013 to May 2014. A total of 200 patients of Rheumatoid Arthritis (RA), diagnosed according to the ACR/EULAR criteria 2010, were included in the study. Laboratory investigations including creatinine, ALT, CBC, TSH and fasting lipid profile (LDL, HDL, and Total cholesterol) were done for all patients. Results: Out of 200 patients, 23 (11.5%) were male and 177 (88.5%) were female. The mean age was 36.31±10.46 years and the mean duration of disease was 3.82±3.03 years. A total of 107 (53.5%) patients had dyslipidemia, and the commonest abnormality was a low HDL, seen in 83 (41.5 %) patients. Conclusion: Dyslipidemia was frequently observed in Rheumatoid Arthritis. This may be considered as a secondary impact of chronic inflammatory state, seen in RA. Lipid abnormalities should be sought at regular intervals, and corrective actions taken to mitigate increased cardiovascular disease risk. PMID:28367205
Leong, Amye L.; Euller-Ziegler, Liana
Patient advocacy is based on the premise that people have the right to make their own choices about their health care. Personal advocacy is centred on the experiential expertise of the individual affected by the condition, whereas group advocacy is grounded on patient-centred strategies and actions. The first patient advocacy groups for arthritis were set up over 20 years ago in the USA and have subsequently spread to many other countries. This paper discusses the growth and impact of personal advocacy as well as recent developments in group advocacy in the Asia-Pacific region, Europe, and North America, in terms of arthritis awareness, research, corporate partnerships, and the Bone and Joint Decade global initiative. PMID:15042233
Węgierska, Małgorzata; Dura, Marta; Blumfield, Einat; Żuchowski, Paweł; Waszczak, Marzena; Jeka, Sławomir
Rheumatoid arthritis (RA) is a chronic systemic connective tissue disease. The development of comorbidities often occurs in the course of RA. One of them is osteoporosis, which has serious social and economic effects and may contribute to the increase in the degree of disability and premature death of the patient. Due to the young age in which RA disease occurs, densitometry (DXA) of the lumbar spine is the basic examination in osteoporosis diagnostics. In the course of RA, much more frequently than in healthy persons of the same age, osteoporotic fractures of vertebral bodies occur, which hinder a correct assessment in the DXA test. Rheumatoid arthritis patients often undergo computed tomography (CT) examination of the abdominal cavity for other medical indications than suspected spinal injury. Then, CT examination may also serve for the assessment of bone density, especially in patients with osteoporotic fractures.
Gåfvels, C; Hägerström, M; Nordmark, B; Wändell, P E
We identified patients with newly diagnosed rheumatoid arthritis (RA) in the ages 18-65 years who needed psychosocial interventions. A total of 123 patients (90 women) were asked to participate, but 19 declined and 4 dropped out early in the study, leaving a total of 100 patients (75 women) in the sample. Questionnaires used were the Epidemiological Investigation on Rheumatoid Arthritis study questionnaire, the Hospital Anxiety and Depression Scale, the Sense of Coherence (SOC) scale, and the General Coping Questionnaire. Interviews showed that 46% of the included 100 patients had psychosocial problems (PSP). One third of them had problems directly related to RA. The rest had problems with their life situation in general, without or reinforced by RA. Compared to patients without psychosocial problems, PSP patients lived in more strained social situations, especially regarding personal finances and social support. More of the PSP patients were anxious, showed lower SOC scores, and also used more emotion-based coping strategies (resignation, protest, isolation and intrusion) and less problem-oriented (minimization). They also had higher scores on depression and more frequently expected that RA would negatively affect their future. PSP patients also experienced a more negative impact of the disease, a finding not confirmed by the sickness activity score judged by the rheumatologist. Thus, early in the course of RA, screening instruments should be used to identify PSP patients. Psychosocial treatment and support by medical social workers skilled in RA care should be offered.
... A Patient / Caregiver Diseases & Conditions Psoriatic Arthritis Psoriatic Arthritis Fast Facts Psoriatic arthritis is a chronic arthritis. ... appear before the skin disorder. What is psoriatic arthritis? Psoriasis is a disease in which scaly red ...
... A Patient / Caregiver Diseases & Conditions Juvenile Arthritis Juvenile Arthritis Fast Facts Arthritis in children is treatable. It ... as fevers or rash. What is juvenile idiopathic arthritis? Several types of arthritis, all involving chronic (long- ...
Thiele, Ralf G
Ultrasonography is an elegant tool for the detection of tenosynovitis, synovitis, and erosions very early in rheumatoid arthritis, and the presence of a power Doppler signal is one of the best predictors of joint damage. Although clinical scores remain the mainstay of disease activity assessment, ultrasonography has proved to be a remarkably robust tool for reliable assessment of changes in rheumatoid arthritis. There is no evidence to suggest that problems with operator dependence would be greater than with other imaging modalities or physical examination, if performed by trained providers.
Do Short and Sustained Periods of American College of Rheumatology/European League Against Rheumatism Remission Predict Functional and Radiographic Outcome in Early Rheumatoid Arthritis Patients With Low Overall Damage Progression?
Konijn, Nicole P C; van Tuyl, Lilian H D; Boers, Maarten; den Uyl, Debby; Ter Wee, Marieke M; Kerstens, Pit; Voskuyl, Alexandre E; van Schaardenburg, Dirkjan; Nurmohamed, Michael T; Lems, Willem F
To investigate whether remission at single and consecutive visits predicts good outcome in early rheumatoid arthritis (RA). The presence of remission according to American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) and other criteria (Boolean clinical, Clinical Disease Activity Index, Disease Activity Score [DAS], DAS in 28 joints, and Routine Assessment of Patient Index Data 3) was assessed in early RA patients during the first year of the Combination Therapy for Rheumatoid Arthritis light trial. Likelihood ratios were used to assess whether meeting the remission criteria at single visits (13, 26, 39, or 52 weeks) and consecutive visits (13 and 26, 26 and 39, or 39 and 52 weeks) predicted good outcome in the second year (52-104 weeks). Good outcome was defined for function (Health Assessment Questionnaire score consistently ≤0.5 and no deterioration), radiographic damage progression (no deterioration in Sharp/van der Heijde scores), and both ("overall good outcome"). Of the original 164 trial patients, 144 had evaluable data. In the second year, good functional outcome was observed in 35%, good radiographic outcome in 79%, and both in 28% of the patients. Almost all criteria predicted good functional and good overall outcome, at both single and consecutive visits; only single DAS remission did not significantly predict good overall outcome (P = 0.07). Sustained remission periods resulted in higher likelihood ratios than remission at single visits. None of the criteria predicted good radiographic outcome. Early RA patients who reached remission according to ACR/EULAR and other criteria during short or sustained periods were likely to retain good physical function in the subsequent months. Sustained remission periods were a stronger predictor than remission at single visits. However, in the setting of low overall damage progression, (sustained) remission was not predictive of good radiographic outcome. © 2016, American College of
Karazincir, Sinem; Akoğlu, Sebahat; Güler, Hayal; Balci, Ali; Babayiğit, Cenk; Eğilmez, Ertuğrul
To investigate pulmonary involvement by high resolution computerized tomography (HRCT) in patients with rheumatoid arthritis (RA) who are asymptomatic and lifelong non-smoker. Twenty-five patients with RA who are asymptomatic and lifelong non-smoker were included in the study. After clinical and laboratory investigations, plain chest X-rays, pulmonary function tests (PFT) and HRCT were performed. End expiratory HRCT slices were obtained for air trapping. Chest X-ray, PFT and HRCT findings showed 12%, 16%, 48% abnormalities, respectively. Interstitial involvement was the most common finding on HRCT (36%) and followed by air trapping (20%). Bronchiectasis, pulmonary nodule, and pleural disease were seen in 16%, 12%, and 12% of patients, respectively. None of patients had emphysema and honeycomb pattern. There was no statistically significant correlation between HRCT findings and disease activity criteria, RF positivity, PFT results and duration of the disease. Our study shows that pulmonary involvement is not always together with respiratory symptoms and impaired pulmonary function in patients with RA. New studies are needed which investigating the effects of radiologically detected lung involvement on prediction of survival and treatment choice in asymptomatic and nonsmoker RA patients.
Scher, Jose U; Joshua, Vijay; Artacho, Alejandro; Abdollahi-Roodsaz, Shahla; Öckinger, Johan; Kullberg, Susanna; Sköld, Magnus; Eklund, Anders; Grunewald, Johan; Clemente, Jose C; Ubeda, Carles; Segal, Leopoldo N; Catrina, Anca I
Airway abnormalities and lung tissue citrullination are found in both rheumatoid arthritis (RA) patients and individuals at-risk for disease development. This suggests the possibility that the lung could be a site of autoimmunity generation in RA, perhaps in response to microbiota changes. We therefore sought to test whether the RA lung microbiome contains distinct taxonomic features associated with local and/or systemic autoimmunity. 16S rRNA gene high-throughput sequencing was utilized to compare the bacterial community composition of bronchoalveolar lavage fluid (BAL) in patients with early, disease-modifying anti-rheumatic drugs (DMARD)-naïve RA, patients with lung sarcoidosis, and healthy control subjects. Samples were further assessed for the presence and levels of anti-citrullinated peptide antibodies (including fine specificities) in both BAL and serum. The BAL microbiota of RA patients was significantly less diverse and abundant when compared to healthy controls, but similar to sarcoidosis patients. This distal airway dysbiosis was attributed to the reduced presence of several genus (i.e., Actynomyces and Burkhordelia) as well as reported periodontopathic taxa, including Treponema, Prevotella, and Porphyromonas. While multiple clades correlated with local and systemic levels of autoantibodies, the genus Pseudonocardia and various related OTUs were the only taxa overrepresented in RA BAL and correlated with higher disease activity and erosions. Distal airway dysbiosis is present in untreated early RA and similar to that detected in sarcoidosis lung inflammation. This community perturbation, which correlates with local and systemic autoimmune/inflammatory changes, may potentially drive initiation of RA in a proportion of cases.
Curtis, Jeffrey R.; Yang, Shuo; Chen, Lang; Park, Grace S.; Bitman, Bojena; Wang, Brian; Navarro-Millan, Iris; Kavanaugh, Arthur
Objective To derive and validate decision trees to categorize rheumatoid arthritis (RA) patients 12 weeks after starting etanercept with or without methotrexate into three groups: patients predicted to achieve low disease activity (LDA) at 1 year; patients predicted to not achieve LDA at 1 year; and patients who needed additional time on therapy to be categorized. Methods Data from RA patients enrolled in TEMPO were analyzed. Classification and Regression Trees were used to develop and validate decision-tree models with week 12 and earlier assessments that predicted long-term LDA. LDA, defined as DAS28 ≤ 3.2 or Clinical Disease Activity Index (CDAI) ≤ 10.0, was measured at 52 or 48 weeks. Demographics, laboratory data, and clinical data at baseline and through week 12 were analyzed as predictors of response. Results Thirty-nine percent (67/172) of patients receiving etanercept and 60% (115/193) of patients receiving etanercept plus methotrexate achieved LDA at week 52. For patients receiving etanercept, 53% were predicted to have LDA, 39% were predicted to not have LDA, and 8% could not be categorized using DAS28 criteria at week 12. For patients receiving etanercept plus methotrexate, 63% were predicted to have LDA, 25% were predicted to not have LDA, and 12% could not be categorized. Conclusion Most (80%–90%) patients in TEMPO initiating etanercept with or without methotrexate could be predicted within 12 weeks of starting therapy as likely to have LDA or not at week 52. However, approximately 10%–20% of patients needed additional time on therapy to decide whether to continue treatment. PMID:21998118
Curtis, Jeffrey R; Yang, Shuo; Chen, Lang; Park, Grace S; Bitman, Bojena; Wang, Brian; Navarro-Millan, Iris; Kavanaugh, Arthur
To derive and validate decision trees to categorise rheumatoid arthritis (RA) patients 12 weeks after starting etanercept with or without methotrexate into three groups: patients predicted to achieve low disease activity (LDA) at 1 year; patients predicted not to achieve LDA at 1 year and patients who needed additional time on therapy to be categorised. Data from RA patients enrolled in the TEMPO trial were analysed. Classification and regression trees were used to develop and validate decision tree models with week 12 and earlier assessments that predicted long-term LDA. LDA, defined as disease activity score in 28 joints (DAS28) ≤3.2 or clinical disease activity index ≤10.0, was measured at 52 or 48 weeks. Demographics, laboratory data and clinical data at baseline and to week 12 were analysed as predictors of response. 39% (67/172) of patients receiving etanercept and 60% (115/193) of patients receiving etanercept plus methotrexate achieved LDA at week 52. For patients receiving etanercept, 53% were predicted to have LDA, 39% were predicted not to have LDA and 8% could not be categorised using DAS28 criteria at week 12. For patients receiving etanercept plus methotrexate, 63% were predicted to have LDA, 25% were predicted not to have LDA and 12% could not be categorised. Most (80-90%) patients in TEMPO initiating etanercept with or without methotrexate could be predicted within 12 weeks of starting therapy as likely to have LDA or not at week 52. However, approximately 10-20% of patients needed additional time on therapy to decide whether to continue treatment.
Ratio of Circulating IFNγ (+) "Th17 Cells" in Memory Th Cells Is Inversely Correlated with the Titer of Anti-CCP Antibodies in Early-Onset Rheumatoid Arthritis Patients Based on Flow Cytometry Methods of the Human Immunology Project.
Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi
Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic joint inflammation characterized by activated T cells. IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. However, it remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we validated the methods of the Human Immunology Project using only the cell-surface marker through measuring the actual expression of IL-17 and IFNγ. We also evaluated the expression of CD161 in human Th17 cells. We then tried to identify Th17 cells, IL-17(+)Th17 cells, and IFNγ (+)Th17 cells in the peripheral blood of early-onset RA patients using the standardized method of the Human Immunology Project. Our findings validated the method and the expression of CD161. The ratio of IFNγ (+)Th17 cells in memory T cells was inversely correlated to the titers of anti-CCP antibodies in the early-onset RA patients. These findings suggest that Th17 cells play important roles in the early phase of RA and that anti-IL-17 antibodies should be administered to patients with early phase RA, especially those with high titers of CCP antibodies.
Golightly, Yvonne M; Marshall, Stephen W; Callahan, Leigh F; Guskiewicz, Kevin
Injury has been identified as a potential risk factor for osteoarthritis. However, no previous study has addressed playing-career injuries and subsequent osteoarthritis in a large sample of former athletes. The purpose of this study was to describe the prevalence and determinants of arthritis and osteoarthritis in retired professional football players. Self-reported arthritis prevalence and retrospectively-recalled injury history were examined in a cross-sectional survey of 2,538 retired football players. Football players reported a high incidence of injury from their professional playing days (52.8% reported knee injuries, 74.1% reported ligament/tendon injuries, and 14.2% reported anterior cruciate ligament tears). For those under 60 years, 40.6% of retired NFL players reported arthritis, compared with 11.7% of U.S. males (prevalence ratio = 3.5, 95% CI: 3.3 to 3.7). Within the retired NFL player cohort, osteoarthritis was more prevalent in those with a history of knee injury (prevalence ratio = 1.7, 95% CI: 1.5 to 1.9) and ligament/tendon injury (prevalence ratio = 1.6, 95% CI: 1.4 to 1.9). In males under the age of 60, arthritis is over 3 times more prevalent in retired NFL players than in the general U.S. population. This excess of early-onset arthritis may be due to the high incidence of injury in football.
Wallace, Carol A.; Giannini, Edward H.; Spalding, Steven J.; Hashkes, Philip J.; O’Neil, Kathleen M.; Zeft, Andrew S.; Szer, Ilona S.; Ringold, Sarah; Brunner, Hermine I.; Schanberg, Laura E.; Sundel, Robert P.; Milojevic, Diana; Punaro, Marilynn G.; Chira, Peter; Gottlieb, Beth S.; Higgins, Gloria C.; Ilowite, Norman T.; Kimura, Yukiko; Hamilton, Stephanie; Johnson, Anne; Huang, Bin; Lovell, Daniel J.
OBJECTIVES To determine if aggressive treatment initiated early in the course of rheumatoid factor positive or negative polyarticular juvenile idiopathic arthritis (poly-JIA) can induce clinical inactive disease (CID) within 6 months. METHODS Between May 2007 and October 2010 a multi-center, prospective, double blind, randomized, placebo controlled trial of two aggressive treatments was conducted in 85 children aged 2 to 16 years with polyarticular JIA of less than 12 months duration. Patients received either methotrexate 0.5 mg/kg/wk SQ (40 mg max), etanercept 0.8 mg/kg/wk (50 mg max), prednisolone 0.5 mg/kg/d (60 mg max) tapered to 0 by 17 weeks (Arm 1), or methotrexate (same dose as Arm 1), etanercept placebo, and prednisolone placebo (Arm 2). The primary outcome was CID at 6 months. An exploratory phase determined the rate of clinical remission on medication (6 months of continuous CID) at 12 months. RESULTS By 6 months, 17 of 42 (40%) of patients in Arm 1 and 10 of 43 (23%) in Arm 2 had achieved CID (X2 = 2.91; p = 0.088). After 12 months, 9 patients in Arm 1 and 3 in Arm 2 achieved clinical remission on medication (p = 0.0534). There were no significant inter-arm differences in adverse events. CONCLUSIONS Although this study did not meet its primary endpoint, early aggressive therapy in this cohort of children with recent onset polyarticular JIA resulted in substantial proportions of patients in both arms achieving CID by 6 months and clinical remission on medication within 12 months of treatment. PMID:22183975
Reina, Delia; Cerdà, Dacia; Güell, Elena; Martínez Montauti, Joaquín; Pineda, Antonio; Corominas, Hèctor
Patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs are susceptible to severe infections such as leishmaniasis. As L. infantum is endemic in the Mediterranean region, it is necessary to rule this infectious process out in any RA patient presenting with fever and pancytopenia. An early diagnosis based on a high suspicion can prevent a fatal outcome. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.
Vernie, Lenneke A.; Rothova, Aniki; v. d. Doe, Patricia; Los, Leonoor I.; Schalij-Delfos, Nicoline E.; de Boer, Joke H.
Background Typically juvenile idiopathic arthritis (JIA)-associated uveitis (further referred as ‘JIA-uveitis’) has its onset in childhood, but some patients suffer its, sometimes visual threatening, complications or ongoing disease activity in adulthood. The objective of this study was to analyze uveitis activity, complications and visual prognosis in adulthood. Methods In this multicenter study, 67 adult patients (129 affected eyes) with JIA-uveitis were retrospectively studied for best corrected visual acuity, visual fields, uveitis activity, topical/systemic treatments, ocular complications, and ocular surgeries during their 18th, 22nd and 30th year of life. Because treatment strategies changed after the year 1990, outcomes were stratified for onset of uveitis before and after 1990. Results Sixty-two of all 67 included patients (93%) had bilateral uveitis. During their 18th life year, 4/52 patients (8%) had complete remission, 28/52 (54%) had uveitis activity and 37/51 patients (73%) were on systemic immunomodulatory treatment. Bilateral visual impairment or legal blindness occurred in 2/51 patients (4%); unilateral visual impairment or legal blindness occurred in 17/51 patients (33%) aged 18 years. The visual prognosis appeared to be slightly better for patients with uveitis onset after the year 1990 (for uveitis onset before 1990 (n = 7) four patients (58%) and for uveitis onset after 1990 (n = 44) 13 patients (30%) were either visual impaired or blind). At least one ocular surgery was performed in 10/24 patients (42%) between their 18th and 22nd year of life. Conclusions Bilateral visual outcome in early adulthood in patients with JIA-uveitis appears to be fairly good, although one third of the patients developed one visually impaired or blind eye. However, a fair amount of the patients suffered from ongoing uveitis activity and needed ongoing treatment as well as surgical interventions. Awareness of these findings is important for ophthalmologists and
Möttönen, T T; Hannonen, P J; Boers, M
A number of reports indicating the growing acceptance of simultaneous therapy with multiple disease-modifying anti-rheumatic drugs (DMARDs), as well as the use of more aggressive treatment measures in the early phases of disease to combat rheumatoid arthritis (RA), have appeared during the last decade. However, only a few randomized controlled clinical trials have been conducted on the use of DMARD combinations in early RA. We review these trials in this article. In two separate one-year studies combination therapy with sulphasalazine (SSZ) and methotrexate (MTX) seemed to offer no benefits compared to either drug used as monotherapy. On the other hand, the DMARD combinations so far proven to be superior to single DMARDs have initially also included a corticosteroid component. In the COBRA study (Combinatietherapie Bij Reumatoide Artritis) the combination of SSZ (2 gm/day), MTX (7.5 mg/week for 40 weeks), and prednisolone (Prd) (initially 60 mg/day, tapered in 6 weekly steps to 7.5 mg/day and stopped after 28 weeks) compared to SSZ alone (2 gm/day) resulted in significantly better clinical outcomes at week 28. Although the difference in clinical response between the treatment arms was lost at week 58, the progression of joint damage remained statistically significantly slower at week 80 in the patients initially assigned to the combination therapy. Furthermore, in the FIN-RACo trial (Finnish Rheumatoid Arthritis Combination Therapy Trial), therapy using a "tailored-steps" strategy with SSZ (1-2 gm/day), MTX (7.5-1.5 mg/week), hydroxychloroquine (300 mg/day), and Prd (up to 10 mg/day) yielded a significantly increased remission rate and less peripheral joint damage at two years than the single DMARD treatment strategy (initially SSZ 2 gm/day), with or without Prd. Adverse effects in both study arms were comparable. Two additional preliminary reports (in abstract form) suggest that intensive local therapy in the form of intra-articular injections added to single or
Citera, Gustavo; Ficco, Hernan Maldonado; Alamino, Rodolfo S Pérez; Pra, Fernando Dal; Lencina, Veronica; Casalla, Luciana; Benegas, Mariana; Rillo, Oscar; Berman, Alberto; Barbaglia, Ana Lucia; Bellomío, Veronica; Salinas, Maria Haye; Alvarez, Ana C; Caeiro, Francisco; Marcos, Josefina; Salas, Adrian; Pellet, Antonio Catalán; Techera, Lorena; Secco, Anastasia; Paira, Sergio; Ceccato, Federico; Bedrán, Zaida; Soriano, Enrique R; Marin, Josefina; Salvatierra, Gabriela; Crespo, Maria Elena
The objective of the study was to evaluate work disability and its main associated factors in patients with early arthritis. Argentine Consortium for Early Arthritis (CONAART) is the first early arthritis cohort in Argentina. Patients with one or more swollen joints and less than 2 years of symptoms duration were followed up prospectively in 13 departments of rheumatology. Social, demographic, familiar, clinical, and laboratory data were recollected. At first year and every year, X-rays of hands and feet were performed and working status and pharmaco-economic data were recollected. Work status (employed, unemployed, retired) and type of work were assessed by direct interview using a predesigned questionnaire. Eight hundred forty-eight patients were included, rheumatoid arthritis (RA) = 483 (57 %)and undifferentiated arthritis (UA) = 365 (43 %), 694 (81.8 %) were women, median age was 46 years (interquartile range (IQR) 35-55.7) and median symptoms duration 7 months (IQR 3-12). Patients with RA had significantly higher disease activity, worse functional capacity and quality of life, and more severe radiological damage compared to UA patients. However work disability (unemployed patient) was comparable between groups (RA = 21 % versus UA = 18.6 % p = NS). In both groups, unemployed patients had higher disease activity score of 28 joints (DAS28), worse Health Assessment Questionnaire (HAQ) values, and less years of formal education (p value <0.005 in all comparisons). Radiological damage was greater in unemployed patients but this difference did not reach statistical significance. In multivariate analysis, disease activity was the main variable associated with unemployment in both groups. Joint involvement was the main cause of work disability in this cohort of patients with early arthritis, independently of the final diagnosis. 1. Work disability is higher in patients with inflammatory arthritis as compared to the general population. 2. Prevalence
Lourdudoss, Cecilia; Wolk, Alicja; Nise, Lena; Alfredsson, Lars; van Vollenhoven, Ronald
Background Dietary intake of vitamin D and omega-3 fatty acids (FA) may be associated with superior response to antirheumatic treatments. In addition, dietary folate intake may be associated with worse response to methotrexate (MTX). The aim of this study was to investigate the association between dietary vitamin D, omega-3 FA, folate and treatment results of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). Methods This prospective study was based on data from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study, and included 727 patients with early RA from 10 hospitals in Sweden. Data on dietary vitamin D, omega-3 FA and folate intake based on food frequency questionnaires were linked with data on European League Against Rheumatism (EULAR) response after 3 months of DMARD treatment. Associations between vitamin D, omega-3 FA, folate and EULAR response were analysed with logistic regression adjusted for potential confounders. Results The majority of patients (89.9%) were initially treated with MTX monotherapy and more than half (56.9%) with glucocorticoids. Vitamin D and omega-3 FA were associated with good EULAR response (OR 1.80 (95% CI 1.14 to 2.83) and OR 1.60 (95% CI 1.02 to 2.53), respectively). Folate was not significantly associated with EULAR response (OR 1.20 (95% CI 0.75 to 1.91)). Similar results were seen in a subgroup of patients who were initially treated with MTX monotherapy at baseline. Conclusions Higher intake of dietary vitamin D and omega-3 FA during the year preceding DMARD initiation may be associated with better treatment results in patients with early RA. Dietary folate intake was not associated with worse or better response to treatment, especially to MTX. Our results suggest that some nutrients may be associated with enhanced treatment results of DMARDs. PMID:28601838
Macovei, Luana-Andreea; Rezuş, Elena
to gather clinical and laboratory data on rheumatoid arthritis patients with cervical spine damage (incidence and prevalence, correlation between duration of disease and the time of lesion onset, to assess signs and symptoms and the role of laboratory investigations). The spine is an axial organ with an important role in support and resistance. It is a pillar with a very complex morphological and functional structure. The vertebral column is crossed by many kinematic chains. The main problem of the cervical spine caused by rheumatoid arthritis is cervical instability which describes all cervical lesions that can lead to neurovascular damage or major disturbance of pain generating statics at movement. The evolving disease shows chronic inflammation of the synovium, which is a self-maintained process and an immunologically induced phenomenon. The chronic inflammation of the synovium forms granulation tissue that invades peripheral joints towards the center and causes ligament cartilage and bone damage. The present paper investigated cervical spine lesions in 107 rheumatoid arthritis patients who were admitted to the 1st Rheumatology Clinic of Iasi Rehabilitation Hospital between January 2013 and December 2014. Our study focused on assessing signs and symptoms seen in spine affected by rheumatic disease. the disease causes destructive lesions due to granulomatous infiltration of rachidian structures and medullary sheaths. These lesions lead to damaged discs and instability that produces subluxations and dislocations. The suboccipital region is most affected; in other regions of the spine, high lesions of C4-C5 prevail, where osteolysis damage of spinal apophyses are found. In atlas and axis joints, rheumatoid arthritis causes the inflammation of bursa, synovium and joint capsule and leads to synovial pannus formation. This causes the destruction of cartilage and subchondral bone. Atlantoaxial dislocation is caused by erosive synovitis of atlanto-epistrophic joint
De Winter, Liesbeth M; Hansen, Wendy L J; van Steenbergen, Hanna W; Geusens, Piet; Lenaerts, Jan; Somers, Klaartje; Stinissen, Piet; van der Helm-van Mil, Annette H M; Somers, Veerle
Despite recent progress in biomarker discovery for RA diagnostics, still over one-third of RA patients-and even more in early disease-present without RF or ACPA. The aim of this study was to confirm the presence of previously identified autoantibodies to novel Hasselt University (UH) peptides in early and seronegative RA. Screening for antibodies against novel UH peptides UH-RA.1, UH-RA.9, UH-RA.14 and UH-RA.21, was performed in two large independent cohorts. Peptide ELISAs were developed to screen for the presence of antibodies to UH-RA peptides. First, 292 RA patients (including 39 early patients), 90 rheumatic and 97 healthy controls from UH were studied. Antibody reactivity to two peptides (UH-RA.1 and UH-RA.21) was also evaluated in 600 RA patients, 309 patients with undifferentiated arthritis and 157 rheumatic controls from the Leiden Early Arthritis Clinic cohort. In both cohorts, 38% of RA patients were seronegative for RF and ACPA. Testing for autoantibodies to UH-RA.1 and UH-RA.21 reduced the serological gap from 38% to 29% in the UH cohort (P = 0.03) and from 38% to 32% in the Leiden Early Arthritis Clinic cohort (P = 0.01). Furthermore, 19-33% of early RA patients carried antibodies to these peptides. Specificities in rheumatic controls ranged from 82 to 96%. Whereas antibodies against UH-RA.1 were related to remission, anti-UH-RA.21 antibodies were associated with inflammation, joint erosion and higher tender and swollen joint counts. This study validates the presence of antibody reactivity to novel UH-RA peptides in seronegative and early RA. This might reinforce current diagnostics and improve early diagnosis and intervention in RA. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: firstname.lastname@example.org.
Zink, A; Listing, J; Niewerth, M; Zeidler, H
OBJECTIVE—To describe current treatment of patients with rheumatoid arthritis (RA) in German rheumatology. METHODS—Data from the German rheumatological database of 1998, comprising clinical and patient questionnaire data of 12 992 outpatients with RA seen at 24 collaborative arthritis centres in Germany, were analysed. RESULTS—At the time of documentation, 88% of the patients with RA were undergoing disease modifying antirheumatic drug (DMARD) treatment. Methotrexate (MTX) was prescribed to 56% of the patients (61% with seropositive and 45% with seronegative RA). Combination treatment was used in 15%. MTX was the drug of first choice even in patients with up to one year's disease duration (49%), followed by antimalarial drugs (21%). Patients treated by non-rheumatologists within the previous year had received DMARD treatment in only 33% of the cases. In steroid treatment, low doses (⩽7.5 mg/day) were used by rheumatologists much more often (44%) than higher doses (12%). 16% of the patients had been inpatients during the previous year, with a median length of stay accumulated over the year of 21 days. Together with stays in inpatient rehabilitation, 22% of all patients had had some form of inpatient treatment. Comprehensive measures such as occupational therapy and patient education were prescribed to fewer than 12% of the patients, mostly during their hospital stay. CONCLUSION—German rheumatologists do follow recent recommendations about early and effective treatment. However, there are still deficits in outpatient care with non-medicinal measures like occupational therapy and patient education, which may partly explain the high hospital admission rates. PMID:11171679
Vance, Michael C.; Packer, Greg; Tan, David; Crisco, J.J. Trey; Wolfe, Scott W.
Midcarpal hemiarthroplasty is a novel motion-preserving treatment for radiocarpal arthritis and is an alternative to current procedures that provide pain relief at the expense of wrist biomechanics and natural motion. It is indicated primarily in active patients with a well-preserved distal row and debilitating arthritic symptoms. By resurfacing the proximal carpal row, midcarpal arthroplasty relieves pain while preserving the midcarpal articulation and the anatomic center of wrist rotation. This technique has theoretical advantages when compared with current treatment options (i.e., arthrodesis and total wrist arthroplasty) since it provides coupled wrist motion, preserves radial length, is technically simple, and avoids the inherent risks of nonunion and distal component failure. The KinematX midcarpal hemiarthroplasty has an anatomic design and does not disrupt the integrity of the wrist ligaments. We have implanted this prosthesis in nine patients with promising early results. The indications for surgery were as follows: scapholunate advanced collapse wrist (three), posttraumatic osteoarthritis (three), inflammatory arthritis (two), and Keinböck disease (one). Prospective data has been collected and the results are preliminary given the infancy of the procedure. The mean follow-up was 30.9 weeks (range: 16 to 56 weeks). The mean Mayo wrist score increased from 31.9 preoperatively to 58.8 (p < 0.05) and the mean DASH score improved significantly from 47.8 preoperatively to 28.7 (p < 0.05). There was a trend toward increased motion but statistical significance was not reached. Two patients required manipulation for wrist stiffness. There was no evidence of prosthetic loosening or capitolunate narrowing. The procedure is simple (average surgical time was 49 minutes) and maintains coupled wrist motion through preservation of the midcarpal articulation. The preliminary data show that it appears safe but considerably longer follow-up is required before
Soósová, Mária Sováriová; Macejová, Želmíra; Zamboriová, Mária; Dimunová, Lucia
Rheumatoid arthritis (RA) is significantly associated with psychiatric morbidity. Mental health conditions are often unrecognized and untreated in primary care. To assess prevalence of anxiety and depression and their impact on arthritis pain and functional disability in Slovak patients with rheumatoid arthritis. Anxiety was assessed by the Beck Anxiety Inventory (BAI), depression by the Zung self-rating depression scale (SDS), pain by the visual analog scale (VAS) and functional disability by the health assessment questionnaire - disability index (HAQ-DI) in 142 patients with rheumatoid arthritis. Spearman's rho was calculated to assess relations between variables. Stepwise linear regression analysis was used to assess impact of anxiety and depression on arthritis pain and functional disability. High prevalence of anxiety and depression was observed in arthritis patients. Anxiety and depression were significant predictors of arthritis pain and functional disability. Sex, education, marital status, disease duration and comorbidity had no impact on arthritis pain and functional disability. These findings support the notions that psychological negative affect can influence subjective perception of arthritis pain and disability. The regular screening of anxiety and depression and the psychological approaches can be useful for managing arthritis patients.
Nieuwenhuis, Wouter P; van Steenbergen, Hanna W; Mangnus, Lukas; Newsum, Elize C; Bloem, Johan L; Huizinga, Tom W J; le Cessie, Saskia; Reijnierse, Monique; van der Helm-van Mil, Annette H M
To assess the diagnostic value of MRI for early RA. In some RA patients, a classifiable diagnosis cannot be made at first presentation; these patients present with unclassified arthritis (UA). The use of MRI for early diagnosis of RA is recommended, yet the evidence for its reliability is limited. MRI of hand and foot was performed in 589 early arthritis patients included in the Leiden Early Arthritis Clinic (229 presented with RA, 159 with other arthritides and 201 with UA). Symptom-free controls provided a reference for defining an abnormal MRI. In preliminary investigations, MRI of patients who presented with RA was compared with MRI of symptom-free controls and of patients with other arthritides. Thereafter, the value of MRI in early RA diagnosis was determined in UA patients using the 1-year follow-up on fulfilling the 1987 RA criteria and start of disease-modifying drugs as outcomes. Preliminary investigations were promising. Of the UA patients, 14% developed RA and 37% started disease-modifying treatment. MRI-detected tenosynovitis was associated with RA development independent of other types of MRI-detected inflammation [odds ratio (OR) = 7.5, 95% CI: 2.4, 23] and also independent of age and other inflammatory measures (swollen joints, CRP) (OR = 4.2, 95% CI: 1.4, 12.9). Within UA patients, the negative predictive value of abnormal tenosynovitis was 95% (95% CI: 89%, 98%) and the positive predictive value 25% (95% CI: 17%, 35%). The performance was best in the subgroup of UA patients presenting with oligoarthritis (18% developed RA): the positive predictive value was 36% (95% CI: 23%, 52%), the negative predictive value was 98% (95% CI: 88%, 100%), the sensitivity was 93% (95% CI: 70%, 99%) and the specificity was 63% (95% CI: 51%, 74%). MRI contributes to the identification of UA patients who will develop RA, mostly in UA patients presenting with oligoarthritis.
Rheumatoid Arthritis (RA) presented at/published to American Pharmacists Association (Journal/Abstract) & American Pharmacists Association Annual...Adherence in Patients with Rheumatoid Arthritis (RA) 6. TITLE OF MATERIAL TO BE PUBLISHED OR PRESENTED: A ssessing Medication A dherence in...Patients with Rheumato id Arthritis (RA) 7. FUNDING RECEIVED FOR THIS STUDY? 0 YES cgj NO FUNDING SOURCE: 8. DO YOU NEED FUNDING SUPPORT FOR PUBLICATION
Tournadre, Anne; Mathieu, Sylvain; Soubrier, Martin
Patients with inflammatory arthritis, such as rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, have higher rates of cardiovascular mortality. While the increased cardiovascular risk is only explained to some extent, a lot of research is currently conducted to improve our understanding of its pathogenesis, risk stratification, and optimal cardiovascular risk management. This review sought to report epidemiological data pertaining to the cardiovascular disease burden in patients with inflammatory arthritis, underlying mechanisms accounting for excessive cardiovascular risk, along with recommendations regarding risk assessment and management in this patient population. PMID:27721904
van Riel, Piet; Alten, Rieke; Combe, Bernard; Abdulganieva, Diana; Bousquet, Paola; Courtenay, Molly; Curiale, Cinzia; Gómez-Centeno, Antonio; Haugeberg, Glenn; Leeb, Burkhard; Puolakka, Kari; Ravelli, Angelo; Rintelen, Bernhard; Sarzi-Puttini, Piercarlo
Treating to target by monitoring disease activity and adjusting therapy to attain remission or low disease activity has been shown to lead to improved outcomes in chronic rheumatic diseases such as rheumatoid arthritis and spondyloarthritis. Patient-reported outcomes, used in conjunction with clinical measures, add an important perspective of disease activity as perceived by the patient. Several validated PROs are available for inflammatory arthritis, and advances in electronic patient monitoring tools are helping patients with chronic diseases to self-monitor and assess their symptoms and health. Frequent patient monitoring could potentially lead to the early identification of disease flares or adverse events, early intervention for patients who may require treatment adaptation, and possibly reduced appointment frequency for those with stable disease. A literature search was conducted to evaluate the potential role of patient self-monitoring and innovative monitoring of tools in optimising disease control in inflammatory arthritis. Experience from the treatment of congestive heart failure, diabetes and hypertension shows improved outcomes with remote electronic self-monitoring by patients. In inflammatory arthritis, electronic self-monitoring has been shown to be feasible in patients despite manual disability and to be acceptable to older patients. Patients' self-assessment of disease activity using such methods correlates well with disease activity assessed by rheumatologists. This review also describes several remote monitoring tools that are being developed and used in inflammatory arthritis, offering the potential to improve disease management and reduce pressure on specialists.
van Riel, Piet; Combe, Bernard; Abdulganieva, Diana; Bousquet, Paola; Courtenay, Molly; Curiale, Cinzia; Gómez-Centeno, Antonio; Haugeberg, Glenn; Leeb, Burkhard; Puolakka, Kari; Ravelli, Angelo; Rintelen, Bernhard; Sarzi-Puttini, Piercarlo
Treating to target by monitoring disease activity and adjusting therapy to attain remission or low disease activity has been shown to lead to improved outcomes in chronic rheumatic diseases such as rheumatoid arthritis and spondyloarthritis. Patient-reported outcomes, used in conjunction with clinical measures, add an important perspective of disease activity as perceived by the patient. Several validated PROs are available for inflammatory arthritis, and advances in electronic patient monitoring tools are helping patients with chronic diseases to self-monitor and assess their symptoms and health. Frequent patient monitoring could potentially lead to the early identification of disease flares or adverse events, early intervention for patients who may require treatment adaptation, and possibly reduced appointment frequency for those with stable disease. A literature search was conducted to evaluate the potential role of patient self-monitoring and innovative monitoring of tools in optimising disease control in inflammatory arthritis. Experience from the treatment of congestive heart failure, diabetes and hypertension shows improved outcomes with remote electronic self-monitoring by patients. In inflammatory arthritis, electronic self-monitoring has been shown to be feasible in patients despite manual disability and to be acceptable to older patients. Patients' self-assessment of disease activity using such methods correlates well with disease activity assessed by rheumatologists. This review also describes several remote monitoring tools that are being developed and used in inflammatory arthritis, offering the potential to improve disease management and reduce pressure on specialists. PMID:27933206
Correlation of 18F-FDG PET/CT assessments with disease activity and markers of inflammation in patients with early rheumatoid arthritis following the initiation of combination therapy with triple oral antirheumatic drugs.
Roivainen, Anne; Hautaniemi, Sannamari; Möttönen, Timo; Nuutila, Pirjo; Oikonen, Vesa; Parkkola, Riitta; Pricop, Luminita; Ress, Rudyard; Seneca, Nicholas; Seppänen, Marko; Yli-Kerttula, Timo
This study evaluated the potential of functional imaging to monitor disease activity and response to treatment with disease-modifying antirheumatic drugs (DMARD) in DMARD-naive patients with early rheumatoid arthritis (RA). The study involved 17 patients with active RA in whom combination therapy was initiated with methotrexate, sulfasalazine, hydroxychloroquine, and low-dose oral prednisolone. Clinical disease activity was assessed at screening, at baseline and after 2, 4, 8 and 12 weeks of therapy. (18)F-FDG PET/CT of all joints was performed at baseline and after 2 and 4 weeks of therapy. (18)F-FDG maximum standardized uptake values showed a reduction of 22 ± 13 % in 76 % of patients from baseline to week 2 and a reduction of 29 ± 13 % in 81 % of patients from baseline to week 4. The percentage decrease in (18)F-FDG uptake from baseline to week 2 correlated with clinical outcome, as measured by the disease activity score (DAS-28) at week 12. In addition, changes in C-reactive protein levels and erythrocyte sedimentation rate were positively associated with changes shown by PET. (18)F-FDG PET/CT findings after 2 and 4 weeks of triple combination oral DMARD therapy correlated with treatment efficacy and clinical outcome in patients with early RA. (18)F-FDG PET/CT may help predict the therapeutic response to novel drug treatments.
... or have trouble moving around, you might have arthritis. Most kinds of arthritis cause pain and swelling in your joints. Joints ... joint can become severely damaged. Some kinds of arthritis can also cause problems in your organs, such ...
Lourenço, Daniela M R; Buscatti, Izabel M; Lourenço, Benito; Monti, Fernanda C; Paz, José Albino; Silva, Clovis A
Optic neuritis (ON) was rarely reported in juvenile idiopathic arthritis (JIA) patients, particularly in those under anti-tumor necrosis factor alpha blockage. However, to our knowledge, the prevalence of ON in JIA population has not been studied. Therefore, 5,793 patients were followed up at our University Hospital and 630 (11%) had JIA. One patient (0.15%) had ON and was reported herein. A 6-year-old male was diagnosed with extended oligoarticular JIA, and received naproxen and methotrexate subsequently replaced by leflunomide. At 11 years old, he was diagnosed with aseptic meningitis, followed by a partial motor seizure with secondary generalization. Brain magnetic resonance imaging (MRI) and electroencephalogram showed diffuse disorganization of the brain electric activity and leflunomide was suspended. Seven days later, the patient presented acute ocular pain, loss of acuity for color, blurred vision, photophobia, redness and short progressive visual loss in the right eye. A fundoscopic exam detected unilateral papilledema without retinal exudates. Orbital MRI suggested right ON. The anti-aquaporin 4 (anti-AQP4) antibody was negative. Pulse therapy with methylprednisolone was administered for five days, and subsequently with prednisone, he had clinical and laboratory improvement. In conclusion, a low prevalence of ON was observed in our JIA population. The absence of anti-AQP4 antibody and the normal brain MRI do not exclude the possibility of demyelinating disease associated with chronic arthritis. Therefore, rigorous follow up is required. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.
T-Helper 17 Cell Cytokine Responses in Lyme Disease Correlate With Borrelia burgdorferi Antibodies During Early Infection and With Autoantibodies Late in the Illness in Patients With Antibiotic-Refractory Lyme Arthritis.
Strle, Klemen; Sulka, Katherine B; Pianta, Annalisa; Crowley, Jameson T; Arvikar, Sheila L; Anselmo, Anthony; Sadreyev, Ruslan; Steere, Allen C
Control of Lyme disease is attributed predominantly to innate and adaptive T-helper 1 cell (TH1) immune responses, whereas the role of T-helper 17 cell (TH17) responses is less clear. Here we characterized these inflammatory responses in patients with erythema migrans (EM) or Lyme arthritis (LA) to elucidate their role early and late in the infection. Levels of 21 cytokines and chemokines, representative of innate, TH1, and TH17 immune responses, were assessed by Luminex in acute and convalescent sera from 91 EM patients, in serum and synovial fluid from 141 LA patients, and in serum from 57 healthy subjects. Antibodies to Borrelia burgdorferi or autoantigens were measured by enzyme-linked immunosorbent assay. Compared with healthy subjects, EM patients had significantly higher levels of innate, TH1, and TH17-associated mediators (P ≤ .05) in serum. In these patients, the levels of inflammatory mediators, particularly TH17-associated cytokines, correlated directly with B. burgdorferi immunoglobulin G antibodies (P ≤ .02), suggesting a beneficial role for these responses in control of early infection. Late in the disease, in patients with LA, innate and TH1-associated mediators were often >10-fold higher in synovial fluid than serum. In contrast, the levels of TH17-associated mediators were more variable, but correlated strongly with autoantibodies to endothelial cell growth factor, matrix metalloproteinase 10, and apolipoprotein B-100 in joints of patients with antibiotic-refractory LA, implying a shift in TH17 responses toward an autoimmune phenotype. Patients with Lyme disease often develop pronounced TH17 immune responses that may help control early infection. However, late in the disease, excessive TH17 responses may be disadvantageous by contributing to autoimmune responses associated with antibiotic-refractory LA.
Disease activity assessment is a cornerstone of monitoring rheumatoid arthritis (RA) development and guidance for rituximab treatment. Beside clinical signs and symptoms biomarkers (RF and anti-CCP) are important early predictors of response to therapy and they can predict disease development. Autoantibody (RF and anti-CCP) seropositivity has been associated with positive response to rituximab (RTX) in antiTNF-IR patients, DMARD-IR patients and MTX-naive patients. Selecting therapy for TNF-IR patients providing most likely response it should be taken in consideration results form recently published assessments demonstrating for RTX treated patients significant improvement in DAS28 from baseline versus alternative TNF inhibitor treatment. Recently published NICE treatment guideline is recommending upon antiTNF failure RTX treatment (in combination with MTX) instead antiTNF cycling.
Musiej-Nowakowska, E.; Ploski, R.
OBJECTIVES—To study interaction of early onset pauciarticular juvenile chronic arthritis (EOP-JCA) and pregnancy in the Polish population, in particular to confirm the ameliorating effect of pregnancy on disease activity reported by others and to analyse the factors that govern the occurrence of postpartum flare, with emphasis on the potential role of breast feeding. METHODS—The reproductive outcome and disease status in 39 adult women with history of EOP- JCA was examined by means of a questionnaire and an interview. In all patients the disease onset occurred before the 6th birthday, 19 had persistent pauciarticular JCA (PeEOP-JCA) and 20 had extended pauciarticular JCA (ExEOP-JCA). RESULTS—23 women had at least one successful pregnancy, seven had unsuccessful pregnancies but all of them had also one or more successful pregnancies. Among those who have never been pregnant (n=16) there was a higher frequency of eye disease and ExEOP-JCA compared with the rest of the group. In almost all cases pregnancy was associated with remission of disease activity, however a postpartum flare appeared after 22 pregnancies (52%). The flares were more frequent in women who had an active disease before pregnancy, had a flare after a previous pregnancy and/or were breast feeding. CONCLUSIONS—In EOP-JCA patients pregnancy generally has a good outcome and induces amelioration of disease activity. After delivery, however, a flare of disease often appears, especially in women who were breast feeding, had a postparum flare previously or had an active disease before pregnancy. The pattern of interaction between disease and pregnancy found in EOP-JCA makes EOP-JCA similar in this respect to RA, but different from systemic lupus erythematosus and ankylosing spondylitis. PMID:10419865
Ishi, Eduardo de Paula; Bertolo, Manoel Barros; Rossa, Carlos; Kirkwood, Keith Lough; Onofre, Mirian Aparecida
The purpose of this clinical study was to investigate if periodontal disease and rheumatoid arthritis (RA) are associated. The study included 39 RA patients (test group) and 22 age- and gender-matched healthy individuals (control group). Questionnaires on general and oral health were applied and a complete periodontal exam, including visible plaque, marginal bleeding, attachment loss (AL) and number of teeth present, was also performed by a single calibrated examiner. Diabetes mellitus patients and smokers were excluded. RA patients had fewer teeth, higher prevalence of sites presenting dental plaque and a higher frequency of sites with advanced attachment loss. Although the prevalence of dental plaque was higher in the test group (Chi-square test, p = 0.0006), the percentage of sites showing gingival bleeding was not different (Fishers exact test, p > 0.05). Based on our results, we suggest that there is an association between periodontal disease and RA.
Tocilizumab combination therapy or monotherapy or methotrexate monotherapy in methotrexate-naive patients with early rheumatoid arthritis: 2-year clinical and radiographic results from the randomised, placebo-controlled FUNCTION trial.
Burmester, Gerd R; Rigby, William F; van Vollenhoven, Ronald F; Kay, Jonathan; Rubbert-Roth, Andrea; Blanco, Ricardo; Kadva, Alysha; Dimonaco, Sophie
Investigate whether the efficacy and safety of intravenous tocilizumab (TCZ) demonstrated at week 52 in patients with early rheumatoid arthritis (RA) are maintained to week 104. Methotrexate (MTX)-naive patients with early progressive RA were randomly assigned to double-blind 4 mg/kg TCZ+MTX, 8 mg/kg TCZ+MTX, 8 mg/kg TCZ+placebo or placebo+MTX for 104 weeks. Patients not receiving 8 mg/kg TCZ and not achieving Disease Activity Score-28 joints (DAS28-erythrocyte sedimentation rate (ESR)) ≤3.2 at week 52 switched to escape therapy (8 mg/kg TCZ+MTX). Analyses were exploratory. Intent-to-treat and safety populations included 1157 and 1153 patients, respectively. DAS28-ESR remission (<2.6) rates were maintained from weeks 52 to 104 (eg, 8 mg/kg TCZ+MTX, 49.3% to 47.6%). Placebo+MTX and 4 mg/kg TCZ+MTX escape patients' week 104 response rates were 51.4% and 30.5%, respectively. Inhibition of radiographic progression was maintained with 8 mg/kg TCZ (eg, 8 mg/kg TCZ+MTX mean (SD) change from baseline in modified total Sharp score: 0.13 (1.28), week 52; 0.19 (2.08), week 104). The safety profile of TCZ was consistent with that of previous reports. Patients with early RA treated with TCZ monotherapy or TCZ+MTX maintained clinical benefits during their second year of treatment with no new safety signals. NCT01007435; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Herasymenko, S I; Huzhevs'kyĭ, I V; Vovchenko, H Ia; Babko, A N
With the purpose of finding out informative value of the ultrasound investigation designed to study the capsular and ligamentous apparatus of the knee joint in its instability during the early stages of rheumatoid arthritis and correlating clinical symptoms with ultrasonographic findings an examination was done of twenty joints of patients in early stages of rheumatoid arthritis presenting with clinical signs of anterior-medial instability. Sonography confirmed the presence of instability and permitted the qualitative assessment of its degree to be done. The method allows us to disclose relative incompetence of the anterior-medial sector of the knee joint in those patients presenting with early stages of rheumatoid arthritis, which is one of causes of instability, with the cruciate and lateral ligaments remaining uninjured. Ultrasonography makes it possible to perform a quantitative assessment of the degree of instability of the joint irrespective of the clinical test used and experience of the orthopedist.
Warmington, Kelly; Kennedy, Carol A; Lundon, Katie; Soever, Leslie J; Brooks, Sydney C; Passalent, Laura A; Shupak, Rachel; Schneider, Rayfel
Objective To assess patient satisfaction with the arthritis care services provided by graduates of the Advanced Clinician Practitioner in Arthritis Care (ACPAC) program. Materials and methods This was a cross-sectional evaluation using a self-report questionnaire for data collection. Participants completed the Patient–Doctor Interaction Scale, modified to capture patient–practitioner interactions. Participants completed selected items from the Group Health Association of America’s Consumer Satisfaction Survey, and items capturing quality of care, appropriateness of wait times, and a comparison of extended-role practitioner (ERP) services with previously received arthritis care. Results A total of 325 patients seen by 27 ERPs from 15 institutions completed the questionnaire. Respondents were primarily adults (85%), female (72%), and living in urban areas (79%). The mean age of participants was 54 years (range 3–92 years), and 51% were not working. Patients with inflammatory (51%) and noninflammatory conditions (31%) were represented. Mean (standard deviation) Patient–Practitioner Interaction Scale subscale scores ranged from 4.50 (0.60) to 4.63 (0.48) (1 to 5 [greater satisfaction]). Overall satisfaction with the quality of care was high (4.39 [0.77]), as was satisfaction with wait times (referral to appointment, 4.27 [0.86]; in clinic, 4.24 [0.91]). Ninety-eight percent of respondents felt the arthritis care they received was comparable to or better than that previously received from other health care professionals. Conclusion Patients were very satisfied with and amenable to arthritis care provided by graduates of the ACPAC program. Our findings provide early support for the deployment and integration of ACPAC ERPs into the Ontario health care system and should inform future evaluation at the patient level. PMID:27790044
Verstappen, S M M; Jacobs, J W G; van der Veen, M J; Heurkens, A H M; Schenk, Y; ter Borg, E J; Blaauw, A A M; Bijlsma, J W J
Background To investigate whether intensive treatment with methotrexate (MTX) according to a strict protocol and a computerised decision program is more beneficial compared to conventional treatment with MTX in early rheumatoid arthritis. Methods In a two‐year multicentre open label strategy trial, 299 patients with early rheumatoid arthritis were randomly assigned to the intensive strategy group or the conventional strategy group. Patients in both groups received MTX, the aim of treatment being remission. Patients in the intensive treatment group came to the outpatient clinic once every month; adjustment of the MTX dosage was tailored to the individual patient on the basis of predefined response criteria, using a computerised decision program. Patients of the conventional strategy group came to the outpatient clinic once every three months; they were treated according to common practice. Cyclosporine was added if patients had an inadequate response to maximal tolerated MTX doses. Results Seventy six (50%) patients in the intensive strategy group achieved at least one period of remission during the two year trial, versus 55 patients (37%) in the conventional strategy group (p = 0.03). Areas under the curve for nearly all clinical variables were significantly lower—that is, there was a better clinical effect for the intensive treatment group compared with the conventional treatment group. Conclusion The results of this study show that it is possible to substantially enhance the clinical efficacy early in the course of the disease by intensifying treatment with MTX, aiming for remission, tailored to the individual patient. Furthermore, participating rheumatologists indicated that the computerised decision program could be a helpful tool in their daily clinical practice. PMID:17519278
This paper reviews recent approaches to treatment of early rheumatoid arthritis (RA) with disease-modifying antirheumatic drugs (DMARDs). The literature on treatment the early RA published between 1995 and 2007 was accessed through the PubMed database from the National Library of Medicine. Keywords were 'early rheumatoid arthritis', 'disease-modifying antirheumatic drugs', 'biologic agents' and 'combination therapy'. Only results of trials on human subjects that directly measured the effects of DMARDs or biological agents on clinical, laboratory parameters and radiological progression of early RA were selected. Combination therapy suppresses RA activity and radiological progression more effectively than monotherapy. If better control of RA is evident after 3-6 months of treatment with the combination of DMARDs, one must still decide whether to stop the first DMARD, stop the second, or continue with the combination. Combination therapy biological agents (infliximab, adalimumab) with methotrexate and etanercept therapy alone may induce remission in many patients with early RA. It is a method of choice in patients with an adverse prognosis. The main indications for combination therapy 'standard' DMARDs or combination 1 DMARDs with a biological agent are such variables as detection of a shared epitope, increase of concentration of anticyclic citrullinated peptide antibodies, rheumatoid factor, C-reactive protein, 28-joint disease activity score, Sharp score and presence of erosion in joints. The majority of rheumatologists believe that patients with RA should be treated with DMARDs earlier rather than later in the disease process. Further trials should establish the optimal approaches to early RA therapy.
Ten Brinck, Robin M; van Steenbergen, Hanna W; Mangnus, Lukas; Burgers, Leonie E; Reijnierse, Monique; Huizinga, Tom Wj; van der Helm-van Mil, Annette Hm
A phase of arthralgia may precede the emergence of rheumatoid arthritis (RA). Although several studies have focused on biomarkers, the relevance of this phase for patients is less studied. It is unknown if patients already have functional limitations and if this is correlated to the extent of subclinical inflammation. Therefore, we assessed functional disability in patients with clinically suspect arthralgia (CSA), its association with MRI-detected subclinical inflammation and its course during progression to clinical arthritis. From April 2012 to March 2015, 241 patients had arthralgia for <1 year and were, based on clinical presentation, considered at risk for RA by their rheumatologists. At baseline, Health Assessment Questionnaire (HAQ) scores were determined and unilateral 1.5 T MRI of metacarpophalangeal, wrist and metatarsophalangeal joints were made. Presence of MRI-detected subclinical inflammation was assessed by summing synovitis, tenosynovitis and bone marrow oedema scores (range 0-189). Patients were followed on arthritis development and HAQ scores were repeated when clinical arthritis had developed. The median HAQ score at presentation with CSA was 0.50. Higher MRI-inflammation scores were associated with higher HAQ scores (β=0.017, 95% CI=0.004 to 0.030). During median 103 weeks follow-up, 44 patients progressed to clinical arthritis. HAQ scores ≥1.0 were associated with arthritis development (HR=2.50, 95% CI=1.03 to 6.10). Within converters, median HAQ scores did not increase from presentation with CSA to arthritis development (0.88 and 0.75, p=0.36). HAQ scores ≥1.0 at presentation were associated with the development of clinical arthritis. Functional limitations in the prearthritis phase of CSA were as serious as in the early clinical phase, demonstrating the relevance of CSA from patients' perspectives.
Leon, Leticia; Redondo, Marta; Garcia-Vadillo, Alberto; Perez-Nieto, Miguel A; Rodriguez-Rodriguez, Luis; Jover, Juan A; Gonzalez-Alvaro, Isidoro; Abasolo, Lydia
Individualized treatment of rheumatoid arthritis (RA) based on genetic/serologic factors is increasingly accepted. Moreover, patients are more actively involved in the management of their disease. However, personality has received little attention with respect to perception of the need and adherence to treatment. Our objective was to evaluate whether patient personality was associated with the acceptance or rejection of more aggressive early treatment. We performed a cross-sectional study in two hospitals with early arthritis clinics where sociodemographic, clinical, and therapeutic variables are systematically recorded. Patients completed Eysenck Personality Questionnaire, Multidimensional Health Locus of Control, Pain-Related Self-Statement Scale and Pain-Related Control Scale. Aggressive treatment was considered if patients received more than two DMARDs or biological agents during the first year of follow-up. Multivariate logistic regression analysis was performed to determine predictors of aggressive treatment. One hundred seventy-six RA patients were included (80 % women, disease begin median age 55 years). Treatment was considered aggressive in 57.9 % of the sample. Scores were high in extraversion in 50.8 % of patients, neuroticism in 29.5 % and psychoticism in 14.7 %. Neuroticism was the only factor associated with aggressive treatment, which was less probable (p = 0.04, OR = 0.40). Neuroticism also decreased the possibility of receiving a combination of biologics and DMARDs (p = 0.04, OR = 0.28). Patients with high scores on neuroticism are more worried, obsessive and hypochondriac, leading them to reject more aggressive therapy. It is important to educate about their disease so that they will accept more aggressive approaches in clear cases of poor outcome.
ten Brinck, Robin M; van Steenbergen, Hanna W; Mangnus, Lukas; Burgers, Leonie E; Reijnierse, Monique; Huizinga, Tom WJ; van der Helm-van Mil, Annette HM
Introduction A phase of arthralgia may precede the emergence of rheumatoid arthritis (RA). Although several studies have focused on biomarkers, the relevance of this phase for patients is less studied. It is unknown if patients already have functional limitations and if this is correlated to the extent of subclinical inflammation. Therefore, we assessed functional disability in patients with clinically suspect arthralgia (CSA), its association with MRI-detected subclinical inflammation and its course during progression to clinical arthritis. Methods From April 2012 to March 2015, 241 patients had arthralgia for <1 year and were, based on clinical presentation, considered at risk for RA by their rheumatologists. At baseline, Health Assessment Questionnaire (HAQ) scores were determined and unilateral 1.5 T MRI of metacarpophalangeal, wrist and metatarsophalangeal joints were made. Presence of MRI-detected subclinical inflammation was assessed by summing synovitis, tenosynovitis and bone marrow oedema scores (range 0–189). Patients were followed on arthritis development and HAQ scores were repeated when clinical arthritis had developed. Results The median HAQ score at presentation with CSA was 0.50. Higher MRI-inflammation scores were associated with higher HAQ scores (β=0.017, 95% CI=0.004 to 0.030). During median 103 weeks follow-up, 44 patients progressed to clinical arthritis. HAQ scores ≥1.0 were associated with arthritis development (HR=2.50, 95% CI=1.03 to 6.10). Within converters, median HAQ scores did not increase from presentation with CSA to arthritis development (0.88 and 0.75, p=0.36). Conclusions HAQ scores ≥1.0 at presentation were associated with the development of clinical arthritis. Functional limitations in the prearthritis phase of CSA were as serious as in the early clinical phase, demonstrating the relevance of CSA from patients’ perspectives. PMID:28879045
Lourdudoss, Cecilia; Wolk, Alicja; Nise, Lena; Alfredsson, Lars; Vollenhoven, Ronald van
Dietary intake of vitamin D and omega-3 fatty acids (FA) may be associated with superior response to antirheumatic treatments. In addition, dietary folate intake may be associated with worse response to methotrexate (MTX). The aim of this study was to investigate the association between dietary vitamin D, omega-3 FA, folate and treatment results of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). This prospective study was based on data from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study, and included 727 patients with early RA from 10 hospitals in Sweden. Data on dietary vitamin D, omega-3 FA and folate intake based on food frequency questionnaires were linked with data on European League Against Rheumatism (EULAR) response after 3 months of DMARD treatment. Associations between vitamin D, omega-3 FA, folate and EULAR response were analysed with logistic regression adjusted for potential confounders. The majority of patients (89.9%) were initially treated with MTX monotherapy and more than half (56.9%) with glucocorticoids. Vitamin D and omega-3 FA were associated with good EULAR response (OR 1.80 (95% CI 1.14 to 2.83) and OR 1.60 (95% CI 1.02 to 2.53), respectively). Folate was not significantly associated with EULAR response (OR 1.20 (95% CI 0.75 to 1.91)). Similar results were seen in a subgroup of patients who were initially treated with MTX monotherapy at baseline. Higher intake of dietary vitamin D and omega-3 FA during the year preceding DMARD initiation may be associated with better treatment results in patients with early RA. Dietary folate intake was not associated with worse or better response to treatment, especially to MTX. Our results suggest that some nutrients may be associated with enhanced treatment results of DMARDs. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless
Espinoza, Francisco; Fabre, Sylvie; Pers, Yves-Marie
Recent guidelines on rheumatoid arthritis (RA) point to the importance of achieving remission as soon as possible during the course of the disease. The appropriate use of antirheumatic drugs is critical, particularly in early RA patients, before 24 weeks, since this is a 'window of opportunity' for treatment to modify disease progression. A treat-to-target strategy added to an aggressive therapeutic approach increases the chance of early remission, particularly in early RA patients. We conducted an overview of current therapeutic strategies leading to remission in early RA patients. We also provide interesting predictive factors that can guide the RA management strategy with regard to disease-modifying treatment and/or drug-free remission.
Espinoza, Francisco; Fabre, Sylvie; Pers, Yves-Marie
Recent guidelines on rheumatoid arthritis (RA) point to the importance of achieving remission as soon as possible during the course of the disease. The appropriate use of antirheumatic drugs is critical, particularly in early RA patients, before 24 weeks, since this is a ‘window of opportunity’ for treatment to modify disease progression. A treat-to-target strategy added to an aggressive therapeutic approach increases the chance of early remission, particularly in early RA patients. We conducted an overview of current therapeutic strategies leading to remission in early RA patients. We also provide interesting predictive factors that can guide the RA management strategy with regard to disease-modifying treatment and/or drug-free remission. PMID:27493689
Troum, Orrin M; Pimienta, Olga; Olech, Ewa
Early diagnosis and treatment have been recognized as essential for improving clinical outcomes in patients with rheumatoid arthritis (RA). Magnetic resonance imaging (MRI) is a sensitive modality that can assess both inflammatory and structural lesions. MRI can assist in following the disease course in patients treated with traditional disease-modifying antirheumatic drugs and biological therapies both in the clinic and in research trials. Therefore, it is anticipated that MRI becomes the diagnostic imaging modality of choice in RA clinical trials while remaining a useful tool for clinicians evaluating patients with RA.
BUCHT, A.; LARSSON, P.; WEISBROT, L.; THORNE, C.; PISA, P.; SMEDEGÅRD, G.; KEYSTONE, E C; GRÖNBERG, A.
The expression of immunoregulatory cytokines was investigated in freshly isolated synovial fluid mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC) from patients with RA, using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay. IFN-γ, TGF-β, IL-10 and IL-12 (p40) transcripts were detected in SFMC of patients with early disease (<1 year duration) as well as in patients with long standing arthritis (>1 year). The expression of IFN-γ, IL-10 and IL-12 mRNA was increased in SFMC compared with RA PBMC. In addition, the expression was higher in RA SFMC than in PBMC from healthy control individuals. Immunoassay analysis of the secreted IL-12 heterodimer demonstrated increased levels in RA SF compared with levels found in serum from RA patients and control individuals. High levels of TGF-β mRNA were found in SFMC, but a significantly decreased TGF-β/β2-microglobulin (β2-M) ratio was found compared with PBMC from both patients and control individuals. IL-4 mRNA could not be detected, either in SFMC or in PBMC. Cytokine expression in RA PBMC did not differ from control PBMC, with the exception of a decreased TGF-β/β2-M ratio in RA patients with early disease. Our findings of IFN-7 mRNA and IL-12, but undetectable levels of IL-4 mRNA, suggest that the synovitis is characterized by a type 1 immune response. The presence of TGF-β and IL-10 mRNA indicates that immunosuppressive cytokines may also operate in the inflamed joint, although their level of expression may not be sufficient for down-modulation of immune activation. PMID:8608632
Jacobs, Johannes W G
The history, main issues and results of the two tight control CAMERA (Computer-Assisted Management in Early Rheumatoid Arthritis) studies are described. The first CAMERA study showed favourable and superior effects of a tight control methotrexate-based strategy, compared to that of a conventional methotrexate-based strategy. In CAMERA-II, the results were even better when adding 10 mg prednisone daily for 2 years to the methotrexate-based, tight control strategy. In all, the CAMERA studies have shown good results in the treatment of early RA patients with conventional anchor drugs, aiming for remission, making use of a feasible and simple computer decision program.
Oliveira, Silvia Cristina Gutierrez; Oliveira, Leda Magalhaes; Jones, Anamaria; Natour, Jamil
The foot and ankle in rheumatoid arthritis undergo highly destructive synovitis with loss of muscle strength. To evaluate the muscle strength of ankles in patients with rheumatoid arthritis based on isokinetic dynamometry parameters. Thirty patients with a diagnosis of rheumatoid arthritis involving the ankle(s) and 30 healthy subjects (control group) matched for age, gender, race, body mass index and lower limb dominance were studied. Dorsiflexion, plantarflexion, inversion and eversion were evaluated in all subjects on an isokinetic Cybex Norm dynamometer. The variables were compared between the rheumatoid arthritis and control groups and between the right and left ankles, and the dorsiflexor/plantar flexor and invertor/evertor muscle strength ratio was determined. Patients with rheumatoid arthritis performed statistically worse in the isokinetic dynamometry test for all ankle movements. The muscle strength ratio between dorsiflexors and plantar flexors was different in the two groups. No significant differences were observed in the invertor and evertor ratios. In the two groups the plantar flexor musculature was statistically stronger than dorsiflexors. We conclude that patients with rheumatoid arthritis perform worse in isokinetic dynamometry regarding all ankle movements than control subjects, with similar isokinetic test results being observed for the right and left side in both groups, with few exceptions. Isokinetic evaluation posed no additional risk such as important pain or inflammatory activity to patients with rheumatoid arthritis. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.
Gossec, L; Dougados, M; Goupille, P; Cantagrel, A; Sibilia, J; Meyer, O; Sany, J; Daures, J; Combe, B
Objective: To determine prognostic factors for remission in early rheumatoid arthritis. Methods: 191 patients with rheumatoid arthritis whose disease duration was less than one year were followed up prospectively for five years. Remission, defined by a disease activity score (DAS) of <1.6, was used as the outcome measure. Baseline clinical, laboratory, genetic, and radiographic data (with radiographic scores determined by Sharp's method, modified by van der Heijde) were obtained. Results: 48 patients (25.1%) fulfilled the remission criteria at the three year follow up visit, and 30 (15.7%) at three and five years. On univariate analysis by Fisher's exact test, remission at three years and persistent remission at five years were closely correlated with baseline DAS values, C reactive protein level, Ritchie score, health assessment questionnaire score, duration of morning stiffness, and to a lesser extent baseline total radiological scores and rheumatoid factor negativity. No significant correlation was found with sex, age, extra-articular manifestations, erythrocyte sedimentation rate, anti-cyclic citrullinated protein antibodies, anti-keratin antibodies, anti-HSP 90, anticalpastatin antibodies, antinuclear antibodies, or HLA-DRB1* genotypes. Logistic regression analysis showed that the baseline independent variables predictive of remission were low DAS, Ritchie score, morning stiffness duration, and total radiographic score. Conclusions: Baseline prognostic factors for remission in early rheumatoid arthritis were mainly clinical markers of disease activity and radiological scores. PMID:15140774
Del Puente, Antonio; Esposito, Antonella; Costa, Luisa; Benigno, Carla; Del Puente, Aurora; Foglia, Francesca; Oriente, Alfonso; Bottiglieri, Paolo; Caso, Francesco; Scarpa, Raffaele
Psoriatic arthritis (PsA) can have peculiar effects on bone, including mechanisms of bone loss such as erosions, but also of bone formation, such as ankylosis or periostitis. The aim of the present study was to describe the prevalence of fractures in patients with PsA as compared to healthy controls and to investigate determinants of fractures among cases. For both cases and controls, radiographs were read to identify vertebral fractures (VF), and the presence of femoral neck or other nonvertebral fractures was obtained from patients' medical history. The prevalence of fragility fractures on radiographic readings did not differ between cases and controls. The number of subjects showing a VF was 33 (36%) among PsA patients and 36 (36%) among controls, with a prevalence of severe VF of 8% among cases and 4% among controls. Controlling for covariates in a logistic model, the only variables showing a significant correlation with the presence of nonvertebral fractures (NVF) were disease duration (p=0.02), age (p=0.03), and bone mineral density at femoral neck (inverse correlation, p=0.04). Fractures should be carefully considered when evaluating the global picture of the patient with PsA for their contribution to the "fragility" profile.
Garza-García, Carlos; Rocío, Sánchez-Santillán; Orea-Tejeda, Arturo; Castillo-Martínez, Lilia; Eduardo, Canseco; López-Campos, José Luis; Keirns-Davis, Candace
Objective. The aim of the study was to describe echocardiographic abnormalities in patients with rheumatoid arthritis, concurrent systemic comorbidities, rheumatologic clinical activity, serologic markers of rheumatoid arthritis, and inflammatory activity. Methods. In an observational, cross-sectional study, rheumatoid arthritis outpatients were included (n = 105). Conventional transthoracic echocardiographic variables were compared between patients with arthritis and non-RA controls (n = 41). For rheumatoid arthritis patients, articular activity and rheumatologic and inflammatory markers were obtained. Results. Ventricular dysfunction was found in 54.3% of the population: systolic (18.1%), diastolic (32.4%), and/or right (24.8%), with lower ejection fraction (P < 0.0001). Pulmonary hypertension was found in 46.9%. Other echocardiographic findings included increased left atrial diameter (P = 0.01), aortic diameter (P = 0.01), ventricular septum (P = 0.01), left ventricular posterior wall (P = 0.013), and right ventricular (P = 0.01) and atrial diameters compared to control subjects. Rheumatoid factor and anti-CCP antibodies levels were significantly elevated in cases with ventricular dysfunction. Angina and myocardial infarction, diabetes, and dyslipidemia were the main risk factors for ventricular dysfunction. Conclusions. Ventricular dysfunction is common in rheumatoid arthritis and associated with longer disease duration and increased serologic markers of rheumatoid arthritis. Screening for cardiac abnormalities should be considered in this kind of patients.
Garza-García, Carlos; Rocío, Sánchez-Santillán; Orea-Tejeda, Arturo; Castillo-Martínez, Lilia; Eduardo, Canseco; López-Campos, José Luis; Keirns-Davis, Candace
Objective. The aim of the study was to describe echocardiographic abnormalities in patients with rheumatoid arthritis, concurrent systemic comorbidities, rheumatologic clinical activity, serologic markers of rheumatoid arthritis, and inflammatory activity. Methods. In an observational, cross-sectional study, rheumatoid arthritis outpatients were included (n = 105). Conventional transthoracic echocardiographic variables were compared between patients with arthritis and non-RA controls (n = 41). For rheumatoid arthritis patients, articular activity and rheumatologic and inflammatory markers were obtained. Results. Ventricular dysfunction was found in 54.3% of the population: systolic (18.1%), diastolic (32.4%), and/or right (24.8%), with lower ejection fraction (P < 0.0001). Pulmonary hypertension was found in 46.9%. Other echocardiographic findings included increased left atrial diameter (P = 0.01), aortic diameter (P = 0.01), ventricular septum (P = 0.01), left ventricular posterior wall (P = 0.013), and right ventricular (P = 0.01) and atrial diameters compared to control subjects. Rheumatoid factor and anti-CCP antibodies levels were significantly elevated in cases with ventricular dysfunction. Angina and myocardial infarction, diabetes, and dyslipidemia were the main risk factors for ventricular dysfunction. Conclusions. Ventricular dysfunction is common in rheumatoid arthritis and associated with longer disease duration and increased serologic markers of rheumatoid arthritis. Screening for cardiac abnormalities should be considered in this kind of patients. PMID:24368945
Dirven, Linda; van den Broek, Marianne; Kroon, Herman M; Grillet, Bernard A M; Han, K Huub; Kerstens, Pit J S M; Huizinga, Tom W J; Lems, Willem F; Allaart, Cornelia F
To determine the prevalence of large-joint damage and the association with small-joint damage in patients with RA after 8 years of low DAS (≤2.4)-targeted treatment with different treatment strategies. Radiological data of 290 patients participating in the BeSt study, a randomized trial comparing initial monotherapy and initial combination therapy strategies, were used. Radiographs of large joints were scored using the Larsen score and of the small joints using the Sharp-van der Heijde score. With multivariate logistic regression analysis, an association between total damage of the small joints and of the large joints was investigated. After 8 years of treatment, damage was observed in 12% of shoulders, 10% of elbows, 26% of wrists, 13% of hips, 18% of knees and 7% of the ankles. Damage in one or more large joints was found in 64% of patients, with a median score of 1. No difference was found between initial monotherapy or combination therapy strategies. There was a significant association between damage progression in small joints and damage to one or more large joints (OR 1.02; 95% CI 1.00-1.04). After 8 years of DAS-targeted treatment in early RA patients, large-joint damage was found in 64% of patients and was associated with small-joint damage. Continued DAS-targeted treatment is probably more important in damage suppression than initial treatment strategy. Patients with more damage to hands and feet also have more damage to the large joints.
REV1E\\\\’ER 50. "E PFlEV101JS EOmC»lS ARE C . E1E ?~e 3 01 3 FlIll!!S D ~.!!fitt Assessing Medication Adherence in Patients with Rheumatoid Arthritis (RA...Background • Rheumatoid arthritis - Affecting 1-3 million Americans - Seventy percent are women - Associated with higher risk of heart disease and stroke...and Objectives Purpose: Assess medication adherence in patients with rheumatoid arthritis Objectives: 1. Primary: Assess whether there is a correlation
Predictive value of autoantibodies from anti-CCP2, anti-MCV and anti-human citrullinated fibrinogen tests, in early rheumatoid arthritis patients with rapid radiographic progression at 1 year: results from the ESPOIR cohort
Degboé, Yannick; Constantin, Arnaud; Nigon, Delphine; Tobon, Gabriel; Cornillet, Martin; Schaeverbeke, Thierry; Chiocchia, Gilles; Nicaise-Roland, Pascale; Nogueira, Leonor; Serre, Guy; Cantagrel, Alain; Ruyssen-Witrand, Adeline
Objectives We compared the ability of antibodies against cyclic citrullinated peptides (anti-CCP2), against mutated citrullinated vimentin (anti-MCV) and against citrullinated fibrinogen (AhFibA) to predict 1 year rapid radiographic progression (RRP; total Sharp score variation ≥5 points), in early rheumatoid arthritis (RA). Methods We analysed 566 patients from the ESPOIR cohort with early RA fulfilling the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria at year 1. We assayed the 3 anticitrullinated peptide antibodies (ACPA) tests on baseline sera. We compared the performance of these 3 ACPA tests to predict first-year RRP, by comparing areas under the receiver operating characteristic curves (ROCs). We assessed the 1 year RRP risk by ACPA titres. We used a logistic multivariate regression to analyse RRP risk in terms either of ACPA positivity or titre: high (>3 times the N cut-off) and low (1 to 3N). Results 145 patients displayed RRP. Areas under the ROCs were similar (0.60) for the 3 tests. High ACPA titres were associated with 1 year RRP, whatever the test was, and with similar ORs. Low+ anti-MCV titres were not associated with 1-year RRP, whereas low+ anti-CCP2 titres (p=0.0226) and low+ AhFibA titres (p=0.0332) were significantly associated. In multivariate analysis, 1 year RRP was associated with anti-CCP2 positivity (p<0.0001), AhFibA positivity (p<0.0001) and high anti-MCV titres (p<0.0001). Conclusions Anti-CCP2 antibodies and AhFibA were predictive of 1 year RRP in early RA whatever their titre was, whereas only high anti-MCV antibody titres were predictive, potentially making them more discriminant to predict 1 year RRP risk. PMID:26635969
Clinical benefit of 1-year certolizumab pegol (CZP) add-on therapy to methotrexate treatment in patients with early rheumatoid arthritis was observed following CZP discontinuation: 2-year results of the C-OPERA study, a phase III randomised trial.
Atsumi, Tatsuya; Tanaka, Yoshiya; Yamamoto, Kazuhiko; Takeuchi, Tsutomu; Yamanaka, Hisashi; Ishiguro, Naoki; Eguchi, Katsumi; Watanabe, Akira; Origasa, Hideki; Yasuda, Shinsuke; Yamanishi, Yuji; Kita, Yasuhiko; Matsubara, Tsukasa; Iwamoto, Masahiro; Shoji, Toshiharu; Togo, Osamu; Okada, Toshiyuki; van der Heijde, Désirée; Miyasaka, Nobuyuki; Koike, Takao
To investigate the clinical impact of 1-year certolizumab pegol (CZP) therapy added to the first year of 2-year methotrexate (MTX) therapy, compared with 2-year therapy with MTX alone. MTX-naïve patients with early rheumatoid arthritis (RA) with poor prognostic factors were eligible to enter Certolizumab-Optimal Prevention of joint damage for Early RA (C-OPERA), a multicentre, randomised, controlled study, which consisted of a 52-week double-blind (DB) period and subsequent 52-week post treatment (PT) period. Patients were randomised to optimised MTX+CZP (n=159) or optimised MTX+placebo (PBO; n=157). Following the DB period, patients entered the PT period, receiving MTX alone (CZP+MTX→MTX; n=108, PBO+MTX→MTX; n=71). Patients who flared could receive rescue treatment with open-label CZP. 34 CZP+MTX→MTX patients and 14 PBO+MTX→MTX patients discontinued during the PT period. From week 52 through week 104, significant inhibition of total modified total Sharp score progression was observed for CZP+MTX versus PBO+MTX (week 104: 84.2% vs 67.5% (p<0.001)). Remission rates decreased after CZP discontinuation; however, higher rates were maintained through week 104 in CZP+MTX→MTX versus PBO+MTX→MTX (41.5% vs 29.3% (p=0.026), 34.6% vs 24.2% (p=0.049) and 41.5% vs 33.1% (p=0.132) at week 104 in SDAI, Boolean and DAS28(erythrocyte sedimentation rate) remission. CZP retreated patients due to flare (n=28) showed rapid clinical improvement. The incidence of overall adverse events was similar between groups. In MTX-naïve patients with early RA with poor prognostic factors, an initial 1 year of add-on CZP to 2-year optimised MTX therapy brings radiographic and clinical benefit through 2 years, even after stopping CZP. NCT01451203. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
van de Sande, Marleen G. H.; de Hair, Maria J. H.; Schuller, Yvonne; van de Sande, Gijs P. M.; Wijbrandts, Carla A.; Dinant, Huib J.; Gerlag, Danielle M.; Tak, Paul P.
Objectives It has been shown in early arthritis cohorts that the 2010 ACR/EULAR criteria for rheumatoid arthritis (RA) enable an earlier diagnosis, perhaps at the cost of a somewhat more heterogeneous patient population. We describe the features of synovial inflammation in RA patients classified according to these new criteria. Methods At baseline, synovial tissue biopsy samples were obtained from disease-modifying antirheumatic drug (DMARD)-naïve early RA patients (clinical signs and symptoms <1 year). Synovial tissue was analyzed for cell infiltration, vascularity, and expression of adhesion molecules. Stained sections were evaluated by digital image analysis. Patients were classified according to the two different sets of classification criteria, autoantibody status, and outcome. Findings Synovial tissue of 69 RA patients according to 2010 ACR/EULAR criteria was analyzed: 56 patients who fulfilled the criteria for RA at baseline and 13 who were initially diagnosed as undifferentiated arthritis but fulfilled criteria for RA upon follow up. The synovium at baseline was infiltrated by plasma cells, macrophages, and T cells as well as other cells, and findings were comparable to those when patients were selected based on the 1987 ACR criteria for RA. There was no clear cut difference in the characteristics of the synovium between RA patients initially diagnosed as undifferentiated arthritis and those who already fulfilled classification criteria at baseline. Conclusion The features of synovial inflammation are similar when the 2010 ACR/EULAR classification criteria are used compared to the 1987 ACR criteria. PMID:22574210
One of the most frequent extra-articular organ manifestations in rheumatoid arthritis (RA) is anemia. As anemia in RA patients may result in severe symptoms and aggravation of other disease manifestations (e.g. arteriosclerosis), the influence on the course of RA is profound. However, the importance of anemia in RA patients is frequently underestimated. The etiology of anemia in RA is complex. Anemia of inflammation (AI) and iron deficiency anemia, alone or in combination are the most frequent forms of anemia in RA. Changes in iron metabolism are the leading causes of anemia in RA patients and mainly induced by the altered synthesis and function of hepcidin and ferroportin. Hepcidin, a peptide produced in the liver and immunocompetent cells, impairs the expression of ferroportin on iron-secreting cells, thus reducing iron bioavailability. The typical changes of iron metabolism and hepcidin synthesis in RA are induced by proinflammatory cytokines, primarily interleukin-6. Hence, the treatment of RA with cytokine antagonists has significant therapeutic implications on anemia in the context of inflammation and impaired iron metabolism.
Wabe, Nasir; Wiese, Michael D
Development of the treat-to-target (T2T) strategy, the process whereby drug therapy is adjusted until the therapeutic goal is achieved, has revolutionized how rheumatoid arthritis (RA) patients are treated. With the advent of T2T, the management of RA is more effective than ever, with the possibility of remission and other favorable clinical and patient-reported outcomes. Effective implementation of a T2T strategy in routine clinical practice mainly depends on the long-term commitment of physician and patient to T2T treatment recommendations. However, as T2T is a complex process involving aggressive early management with several steps of therapy modifications requiring frequent close monitoring of disease activity and drug toxicities, it may be more liable to suboptimal adherence in real-life clinical practice. The aim of the review is to present key issues related to patient medication adherence and physician adherence to the current RA treatment recommendations and their importance in optimizing the outcome of treatment in RA treated according to T2T strategy.
Salaffi, F; Bazzichi, L; Stancati, A; Neri, R; Cazzato, M; Consensi, A; Grassi, W; Bombardieri, S
To develop a self-administered questionnaire, the ROAD (Recent-Onset Arthritis Disability), to probe physical disability in Italian patients with early arthritis (EA) of less than one year's duration. The development of the ROAD follows a series of major steps: (1) identification of a specific patient population, (2) item pool development, (3) item reduction, (4) internal consistency, (5) pre-testing of the prototype instrument, and (6) a validation study which results in determination, reliability, validity and responsiveness. In this study we have verified the first five steps. Pre-defined areas of disability were culled from eight existing Italian version arthritis-specific questionnaires, and three generic global health measurement tools. Semi-structured interviews helped to derive a 76-item pool from an initial group of 122 items. This questionnaire was administered to 78 EA patients. For scale generation, a combination of frequency importance product (FIP = frequency x mean relevance score) and factor analysis was applied. The top 20 items based on the FIP were then subjected to further analysis. Each question was correlated with every other question. This allowed us to eliminate 8 questions that were therefore highly correlated and were measuring the same concept. The final instrument has 12 items, representing a combination of symptoms that are common, frequently recurring and of general importance to EA patients. Factor analysis provides a 3-factor health status model explaining 70.1% of the variance. The upper extremity function (5 items) is loaded on the first factor, which explains 45.4% of the total measured variance. The lower extremity function (4 items) formed the second factor (14.2% of the total variance). The third factor was determined by activities of daily living/work (3 items) and explain 10.5% of the total variance. The score of the different subscales can be presented graphically as a ROAD profile. Using a traditional development strategy
The first double-blind, randomised, parallel-group certolizumab pegol study in methotrexate-naive early rheumatoid arthritis patients with poor prognostic factors, C-OPERA, shows inhibition of radiographic progression.
Atsumi, Tatsuya; Yamamoto, Kazuhiko; Takeuchi, Tsutomu; Yamanaka, Hisashi; Ishiguro, Naoki; Tanaka, Yoshiya; Eguchi, Katsumi; Watanabe, Akira; Origasa, Hideki; Yasuda, Shinsuke; Yamanishi, Yuji; Kita, Yasuhiko; Matsubara, Tsukasa; Iwamoto, Masahiro; Shoji, Toshiharu; Okada, Toshiyuki; van der Heijde, Désirée; Miyasaka, Nobuyuki; Koike, Takao
To evaluate efficacy and safety of combination therapy using certolizumab pegol (CZP) and methotrexate (MTX) as first-line treatment for MTX-naive, early rheumatoid arthritis (RA) with poor prognostic factors, compared with MTX alone. MTX-naive, early RA patients with ≤12 months persistent disease, high anti-cyclic citrullinated peptide, and either rheumatoid factor positive and/or presence of bone erosions were enrolled in this multicentre, double-blind, randomised placebo (PBO)-controlled study. Patients were randomised 1:1 to CZP+MTX or PBO+MTX for 52 weeks. Primary endpoint was inhibition of radiographic progression (change from baseline in modified Total Sharp Score (mTSS CFB)) at week 52. Secondary endpoints were mTSS CFB at week 24, and clinical remission rates at weeks 24 and 52. 316 patients randomised to CZP+MTX (n=159) or PBO+MTX (n=157) had comparable baseline characteristics reflecting features of early RA (mean disease duration: 4.0 vs 4.3 months; Disease Activity Score 28-joint assessment (DAS28)) (erythrocyte sedimentation rate (ESR)): 5.4 vs 5.5; mTSS: 5.2 vs 6.0). CZP+MTX group showed significantly greater inhibition of radiographic progression relative to PBO+MTX at week 52 (mTSS CFB=0.36 vs 1.58; p<0.001) and week 24 (mTSS CFB=0.26 vs 0.86; p=0.003). Clinical remission rates (Simple Disease Activity Index, Boolean and DAS28 (ESR)) of the CZP+MTX group were significantly higher compared with those of the PBO+MTX group, at weeks 24 and 52. Safety results in both groups were similar, with no new safety signals observed with addition of CZP to MTX. In MTX-naive early RA patients with poor prognostic factors, CZP+MTX significantly inhibited structural damage and reduced RA signs and symptoms, demonstrating the efficacy of CZP in these patients. (NCT01451203). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Alves, Celina; Luime, Jolanda Jacoba; van Zeben, Derkjen; Huisman, Anne-Margriet; Weel, Angelique Elisabeth Adriana Maria; Barendregt, Pieternella Johanna; Hazes, Johanna Maria Wilhelmina
An ACR/EULAR task force released new criteria to classify rheumatoid arthritis at an early stage. This study evaluates the diagnostic performance of these criteria and algorithms by van der Helm and Visser in REACH. Patients with symptoms ≤12 months from REACH were used. Algorithms were tested on discrimination, calibration and diagnostic accuracy of proposed cut-points. Two patient sets were defined to test robustness; undifferentiated arthritis (UA) (n=231) and all patients including those without synovitis (n=513). The outcomes evaluated were methotrexate use and persistent disease at 12 months. In UA patients all algorithms had good areas under the curve 0.79, 95% CI 0.73 to 0.83 for the ACR/EULAR criteria, 0.80, 95% CI 0.74 to 0.87 for van der Helm and 0.83, 95% CI 0.77 to 0.88 for Visser. All calibrated well. Sensitivity and specificity were 0.74 and 0.66 for the ACR/EULAR criteria, 0.1 and 1.0 for van der Helm and 0.59 and 0.93 for Visser. Similar results were found in all patients indicating robustness. The ACR/EULAR 2010 criteria showed good diagnostic properties in an early arthritis cohort reflecting daily practice, as did the van der Helm and Visser algorithms. All were robust. To promote uniformity and comparability the ACR/EULAR 2010 criteria should be used in future diagnostic studies.
Hirata, Shintaro; Tanaka, Yoshiya
To date, the significance of early intervention with methotrexate and biological disease-modifying anti-rheumatic drugs for rheumatoid arthritis (RA) has not been realized. Longitudinal safety and cost have arisen as new concerns. The concept of a treatment holiday, drug discontinuation after achieving remission, may solve these problems. The authors performed a systematic literature review and identified 13 reports from 10 studies (TNF20, BeSt, OPITMA, HIT-HARD, IMPROVED, PRIZE, IDEA, EMPIRE, tREACH and AVERT) for early RA (≤2 years). Eight out of 13 reports (61.5%) were published in 2013 or 2014, indicating emerging interest in recent years. Also, the authors performed a sub-analysis of the HONOR study (n = 51) to compare early (≤2 years) and established RA. The proportions of remission (REM) and low disease activity were higher in early RA (REM: 63.0 vs 33.3%, p = 0.0346; low disease activity: 77.8 vs 45.8%, p = 0.0185). In conclusion, early intervention is beneficial for successful treatment holiday, which may lead to risk and cost reduction. However, further investigation is required.
Faria, Alvaro Camilo Dias; Barbosa, Wellington Ribeiro; Lopes, Agnaldo José; da Rocha Castelar Pinheiro, Geraldo; de Melo, Pedro Lopes
OBJECTIVES: Pulmonary involvement in rheumatoid arthritis is directly responsible for 10% to 20% of all mortality. The best way to improve the prognosis is early detection and treatment. The forced oscillation technique is easy to perform and offers a detailed exam, which may be helpful in the early detection of respiratory changes. This study was undertaken to (1) evaluate the clinical potential of the forced oscillation technique in the detection of early respiratory alterations in rheumatoid arthritis patients with respiratory complaints and (2) to compare the sensitivity of forced oscillation technique and spirometric parameters. METHODS: A total of 40 individuals were analyzed: 20 healthy and 20 with rheumatoid arthritis (90% with respiratory complaints). The clinical usefulness of the parameters was evaluated by investigating the sensibility, the specificity and the area under the receiver operating characteristic curve. ClinicalTrials.gov: NCT01641705. RESULTS: The early adverse respiratory effects of rheumatoid arthritis were adequately detected by the forced oscillation technique parameters, and a high accuracy for clinical use was obtained (AUC>0.9, Se = 80%, Sp = 95%). The use of spirometric parameters did not obtain an appropriate accuracy for clinical use. The diagnostic performance of the forced oscillation technique parameters was significantly higher than that of spirometry. CONCLUSIONS: The results of the present study provide substantial evidence that the forced oscillation technique can contribute to the easy identification of initial respiratory abnormalities in rheumatoid arthritis patients that are not detectable by spirometric exams. Therefore, we believe that the forced oscillation technique can be used as a complementary exam that may help to improve the treatment of breathing disorders in rheumatoid arthritis patients. PMID:23018292
Verhoeven, Frank; Tordi, Nicolas; Prati, Clément; Demougeot, Céline; Mougin, Fabienne; Wendling, Daniel
Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disease and is associated with an excess risk of cardiovascular disease. For the general population, the World Health Organization has issued detailed recommendations on the type of physical activity appropriate for decreasing the cardiovascular risk. The objective of this work is to review available data on the effects of physical activity in patients with RA. RA is responsible for a marked decrease in physical activity. Physical activity significantly diminishes both the cardiovascular risk and the DAS 28. Vascular benefits from physical activity include improved endothelial function and slowing of the atherosclerotic process. Physical activity also has favorable effects on bone, slowing radiographic disease progression in small joints and increasing bone mineral density at the femoral neck, although these effects are not statistically significant. Finally, engaging in physical activity increases self-esteem, alleviates symptoms of depression, improves sleep quality, and decreases pain perception. Aerobic exercise is the most commonly advocated type of physical activity. Most interventions were of short duration (4 weeks) and involved aerobic activity (running or cycling) for 60minutes a day 5 days a week. Resistance training has been shown to decrease systemic inflammation and increase muscle strength. The main obstacles to physical activity in patients with RA are related to both the patients, who lack both motivation and knowledge, and the rheumatologists, who also lack knowledge and place insufficient emphasis on promoting physical activity. Physical activity provides many benefits in patients with RA and should be widely performed. Promoting physical activity should be among the objectives of therapeutic patient education for RA. Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.
Wu, Yu; Zhang, Guojian; Wang, Xiangcheng; Zhao, Zhenfang; Wang, Tao; Wang, Xuemei; Li, Xiao-Feng
To validate 99mTc-labeled arginylglycylaspartic acid (99mTc-3PRGD2) scintigraphy as a means to image synovial neoangiogenesis in joints afflicted by rheumatoid arthritis and to investigate its potential in the early detection and management of rheumatoid arthritis. Rheumatoid arthritis and osteoarthritis were generated in Sprague Dawley rats by type II collagen immunization and papain injection, respectively. Rats were imaged with 99mTc-3PRGD2 and 99mTc- methyl diphosphonate (99mTc MDP). X-ray images were also obtained and assessed by a radiologist. Immunohistochemistry of αvβ3 and CD31confirmed the onset of synovial neoangiogenesis. The effect of bevacizumab on rheumatoid arthritis was followed with 99mTc-3PRGD2 scintigraphy. A patient with rheumatoid arthritis and a healthy volunteer were scanned with 99mTc-3PRGD2. Two weeks after immunization, a significant increase in 99mTc-3PRGD2 was observed in the joints of the rheumatoid arthritis model though uptake in osteoarthritis model and untreated controls was low. 99mTc-MDP whole body scans failed to distinguish early rheumatoid arthritis joints from healthy controls. The expression of αvβ3 and CD31was significantly higher in the joints of rheumatoid arthritis rats compared to normal controls. In serial 99mTc-3PRGD2 scintigraphy studies, 99mTc-3PRGD2 uptake increased in parallel with disease progression. Bevacizumab anti-angiogenetic therapy both improved the symptoms of the rheumatoid arthritis rats and significantly decreased 99mTc-3PRGD2 uptake. Significantly higher 99mTc-3PRGD2 accumulation was also observed in rheumatoid arthritis joints in the patient. Our findings indicate that 99mTc-3PRGD2 scintigraphy could detect early rheumatoid arthritis by imaging the associated synovial neoangiogenesis, and may be useful in disease management.
Intensive combination treatment regimens, including prednisolone, are effective in treating patients with early rheumatoid arthritis regardless of additional etanercept: 1-year results of the COBRA-light open-label, randomised, non-inferiority trial.
ter Wee, Marieke M; den Uyl, Debby; Boers, Maarten; Kerstens, Pit; Nurmohamed, Mike; van Schaardenburg, Dirkjan; Voskuyl, Alexandre E; Lems, Willem F
Recently, we documented the likely non-inferiority of Combinatietherapie Bij Reumatoïde Artritis (COBRA)-light therapy (methotrexate increased to 25 mg/week with initial prednisolone 30 mg/day) compared with the original COBRA therapy (methotrexate 7.5 mg/week, sulfasalazine 2 g/day, with initial prednisolone 60 mg/day) after 26 weeks in patients with early active rheumatoid arthritis (RA). To assess the non-inferiority of COBRA-light versus COBRA after 1 year in terms of disease activity (DAS44), functional outcome (Health Assessment Questionnaire (HAQ)) and radiographic progression (Sharp/van der Heijde score (SHS)), and to assess the effect of adding etanercept. An open-label, randomised controlled, non-inferiority trial of 162 patients with active early RA, following a treat-to-target protocol incorporating the addition of etanercept if DAS44 ≥1.6 at weeks 26 or 39. Both groups showed major improvements in DAS44 after 52 weeks: mean (SD) -2.41 (1.2) in the COBRA and -2.02 (1.0) in the COBRA-light group (p=ns). In both groups, functional ability improved and radiological progression of joints was minimal. At least one adverse event was reported in 96% of the patients in both groups. In total, 25 serious adverse events occurred: 9 vs 16 in COBRA and COBRA-light, respectively. Treatment actually instituted was often less intensive than required by the protocol: of the total population, 108 patients (67%) required etanercept (more in the COBRA-light group), but only 67 of these (62%) actually received it. Intensive COBRA or COBRA-light therapy has major, comparably favourable effects on disease activity, functional ability and radiological outcome after 1 year in patients with early RA. Protocolised addition of etanercept was often not implemented by treating rheumatologists, and patients receiving it appeared to have limited added benefit, probably because of low disease activity levels at its initiation. ISRCTN55552928. Published by the BMJ
van Venrooij, Walther J; van Beers, Joyce J B C; Pruijn, Ger J M
Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation of synovial joints. In most cases this will lead to the formation of pannus tissue, ultimately leading to joint destruction. Early diagnosis, coupled with aggressive use of disease-modifying antirheumatic drugs, has been shown to have a favorable effect on the course of the disease. Therefore, early and accurate diagnosis has become increasingly important. Several sets of criteria have been published to achieve such an early diagnosis, and all of them include measurement of antibodies directed to citrullinated peptides or proteins. This review summarizes our present knowledge about the most well-known and established test to measure these antibodies, the anti-CCP test, which measures antibodies directed to cyclic citrullinated peptides. We describe the current views on how these antibodies are generated and how genetic and environmental parameters are important in this process. The anti-CCP test is more specific than the commonly used RF test (95% versus less than 90%) and has a comparable sensitivity (more than 70%). These antibodies are detectable very early in the disease and are reported to predict the development of erosive RA. Increasing evidence supports a role for these antibodies in the pathology of the disease. In conclusion, testing for anti-CCP autoantibodies is widely accepted as an indispensable tool for diagnosis and early treatment in the management of rheumatoid arthritis patients.
Chandrashekara, S; Shobha, Vineeta; Dharmanand, B G; Jois, Ramesh; Kumar, Sharath; Mahendranath, Kurugodu M; Haridas, Vikram; Prasad, Shiva; Singh, Yogesh; Daware, Manisha A; Swamy, Anupama; Subramanian, R; Somashekar, Srirama A; Shanthappa, Arun M; Anupama, K R
To study the prevalence of remission in rheumatoid arthritis (RA) patients and the influence of different factors like literacy, socioeconomic status, presence of comorbidity and treatment strategy in achieving remission. The study involved 1990 RA patients who were recruited for the Karnataka Rheumatoid arthritis comorbidity (KRAC) study. Based on the factors evaluated, the study participants were classified as follows: age, < 30 years, 30-39 years, 40-49 years, 50-59 years and ≥ 60 years; educational status, illiterate/no formal education, high school or less, graduate, post-graduate and doctorate; family income (₹ per annum), < 50 000, 50-100 000, 100-500 000, and > 500 000; duration of illness prior (DOIP): ≤ 6 months, 6-24 months, 24-120 months and > 120 months. Joint counts were performed by a rheumatologist or trained joint assessor. To assess the treatment outcome, the disease activity score was calculated using the Disease activity Score of 28 joints - erythrocyte sedimentation rate (DAS 28-3 ESR). As per the DAS 28-3 ESR score, around 20% (n = 397) of the study subjects achieved remission. The corresponding mean ± SD of DAS 28-3 ESR noted for remission and non-remission groups were 2.13 ± 0.42 and 4.32 ± 1.28. The majority of the patients were treated with double disease-modifying anti-rheumatic drugs (DMARDs) (60.7%). The likelihood of remission was found to be more in patients who reported DOIP ≤ 6 months. Furthermore, the chances of remission reduced with increase in patient's age and the highest remission rate was noted for 30-39 years age group (59%), followed by 40-49 years (35.4%) and 50-59 years (19.7%). The prevalence of remission noted was around 20%. Early treatment, escalating dose of DMARDs, and patient counseling are important contributing factors for attaining remission. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.
Lee, Ji Eun; Kim, In Je; Cho, Min Sun; Lee, Jisoo
Rheumatoid vasculitis is a rare, but most serious extra-articular complications of long-standing, seropositive rheumatoid arthritis (RA). Vasculitis of hepatic artery is an extremely rare but severe manifestation of rheumatoid vasculitis. A 72-year-old woman who presented with polyarthralgia for 2 months was diagnosed with early RA. Since she had manifestations of livedo reticularis, and liver dysfunction which was atypical for RA patients, a percutaneous needle liver biopsy was performed revealing arteritis of a medium-sized hepatic artery. Extensive investigations did not reveal evidences of other systemic causes such as malignancy or systemic vasculitis. The patient was diagnosed with rheumatoid vasculitis involving hepatic arteries based on Bacon and Scott criteria for rheumatoid vasculitis. With high dose corticosteroid and cyclophosphamide induction and methotrexate and tacrolimus maintenance treatment, she was successfully recovered. Association of rheumatoid vasculitis at very early stages of the disease may represent an early aggressive form of RA. © 2017 The Korean Academy of Medical Sciences.
Abdellatif, Abdul A; Elkhalili, Naser
Chronic kidney disease (CKD) is a comorbid condition that affects, based on recent estimates, between 47% and 54% of patients with gouty arthritis. However, data from randomized controlled trials in patients with gouty arthritis and CKD are limited, and current gouty arthritis treatment guidelines do not address the challenges associated with managing this patient population. Nonsteroidal anti-inflammatory drugs and colchicine are recommended first-line treatments for acute gouty arthritis attacks. However, in patients with CKD, nonsteroidal anti-inflammatory drugs are not recommended because their use can exacerbate or cause acute kidney injury. Also, colchicine toxicity is increased in patients with CKD, and dosage reduction is required based on level of kidney function. Allopurinol, febuxostat, and pegloticase are all effective treatments for controlling elevated uric acid levels after the treatment of an acute attack. However, in patients with CKD, required allopurinol dosage reductions may limit efficacy; pegloticase requires further investigation in this population, and febuxostat has not been studied in patients with creatinine clearance<30 mL/min. This article reviews the risks and benefits associated with currently available pharmacologic agents for the management of acute and chronic gouty arthritis including urate-lowering therapy in patients with CKD. Challenges specific to primary care providers are addressed, including guidance to help them decide when to collaborate with, or refer patients to, rheumatology and nephrology specialists based on the severity of gout and CKD.
Aoki, Takatoshi; Yamashita, Yoshiko; Saito, Kazuyoshi; Tanaka, Yoshiya; Korogi, Yukunori
Forty-one consecutive unclassified arthritis patients with polyarthralgia including wrist joint were evaluated with 3-T MRI as possible early-stage rheumatoid arthritis (RA). After prospective follow-up, 21 of 41 patients fulfilled the American College of Rheumatology (ACR) criteria. Synovitis was detected in all 21 RA patients (sensitivity=100%) with postcontrast MRI and in 14 patients (67%) with unenhanced MRI when none of them fulfilled ACR diagnostic criteria. Fat-suppressed intermediate-weighted fast spin-echo (FSE) image showed high detection rate of synovitis and bone erosion, whereas FIESTA image clearly delineated joint fluid and bone trabeculae. MRI at 3 T is a potentially powerful tool for discriminating and managing early-stage RA patients.
Xu, J; Liu, J; Zhu, L; Zhang, X W; Li, Z G
To explore the titer of glucose-6-phosphate isomerase (GPI) for early diagnosis of the outpatient with rheumatoid arthritis (RA) in real life, and to analyze its relationship with disease activity. In the study, 1 051 patients with arthritis were collected in the group who had joints tender and swelling, and 90 cases of healthy people as a control group. ELISA method was used to detect the serum level of GPI, and according to clinical features and laboratory test, all the patients including 525 RA patients, the other patients including osteoarthritis (OA), 134 cases of seronegative spine joint disease (SpA), 104 cases of systemic lupus erythematosus (SLE), 31 cases of primary Sjogren syndrome (pSS), 24 cases of gout arthritis (GA), 22 cases of other connective tissue diseases (including polymyalgia rheumatica, dermatomyositis, systemic sclerosis, adult Still disease) and 46 cases of other diseases (including 165 cases of osteoporosis, avascular necrosis of the femoral head, traumatic osteomyelitis, bone and joint disease, juvenile rheumatoid arthritis, tumor). The diagnostic values of GPI were assessed, and the differences between the GPI positive and negative groups of the RA patients in clinical characteristics, disease activity, severity and inflammatory index analyzed. The positive rate of serum GPI in the patients with RA was 55.4%, contrasting to other autoimmune diseases (14.3%) and healthy controls (7.78%)(P<0.001). Compared with the OA and SpA patients, the RA group was increased more significantly, and the difference was statistically significant (P<0.001). The diagnostic value of GPI alone for RA was 0.39 mg/L, the sensitivity was 54.2%, and specificity was 87.3%. The positive rate of GPI in RF negative patients was 36.1%; the positive rate of GPI in anti-CCP antibody negative patients was 34.2%; the positive rate of GPI in RF and anti-CCP antibody negative patients was 24.1%. The level of GPI had positive correlation (P<0.05) with ESR, RF, anti
Martínez, Carmen; Ortiz, Ana M.; Juarranz, Yasmina; Lamana, Amalia; Seoane, Iria V.; Leceta, Javier; García-Vicuña, Rosario
Objective Suitable biomarkers are essential for the design of therapeutic strategies in personalized medicine. Vasoactive intestinal peptide (VIP) has demonstrated immunomodulatory properties in autoimmune murine and ex vivo human models. Our aim was to study serum levels of VIP during the follow-up of an early arthritis (EA) cohort and to analyze its value as a biomarker predicting severity and therapeutic requirements. Methods Data from 91 patients on an EA register were analyzed (76% rheumatoid arthritis (RA), 24% undifferentiated arthritis, 73% women, and median age 54 years; median disease duration at entry, 5.4 months). We collected per protocol sociodemographic, clinical, and therapeutic data. VIP levels were determined by enzyme immunoassay in sera harvested from the 91 patients (353 visits; 3.9 visit/patient) and from 100 healthy controls. VIP values below the 25th percentile of those assessed in healthy population were considered low. To determine the effect of independent variables on VIP levels, we performed a longitudinal multivariate analysis nested by patient and visit. A multivariate ordered logistic regression was modeled to determine the effect of low VIP serum levels on disease activity at the end of follow-up. Results VIP concentrations varied considerably across EA patients. Those fulfilling the criteria for RA had the lowest values in the whole sample, although no significant differences were observed compared with healthy donors. Disease activity, which was assessed using DAS28, inversely correlated with VIP levels. After a two-year follow-up, those patients with low baseline levels of VIP displayed higher disease activity and received more intensive treatment. Conclusion Patients who are unable to up-regulate VIP seem to have a worse clinical course despite receiving more intense treatment. Therefore, measurement of VIP levels may be suitable as a prognostic biomarker. PMID:24409325
Hua, Charlotte; Daien, Claire I; Combe, Bernard; Landewe, Robert
Objective To update the evidence pertaining to the diagnosis, prognosis and classification of patients with early arthritis (EA), and to inform the 2016 European League Against Rheumatism (EULAR) recommendations for the management of patients with EA. Methods MEDLINE, EMBASE and Cochrane databases were searched up to October 2015. The first part of the systematic literature review (SLR) involved a search for studies investigating the recognition and referral of EA. The second part involved a search for studies to identify the place of laboratory and imaging tests in establishing a diagnosis and a prognosis in patients with EA. Results Regarding the issue of referral of patients with EA (1643 hits), 4 studies were included. These studies were in support of early referral for patients with EA. Regarding the issue of diagnosis and prognosis of patients with EA (11 435 hits), 88 studies were included, evaluating mainly the value of rheumatoid factor (RF) and anticitrullinated-peptide antibodies (ACPAs). Sensitivity of these antibodies for a RA diagnosis in patients with EA was moderate (40–80%). Specificity was higher, notably for ACPAs (frequently >80%). ACPAs also showed better prognostic performance than RF (negative predictive values around 80%). We confirmed that structural damage on baseline X-rays is predictive of further radiographic progression in patients with EA. Regarding other imaging modalities, data are sparse. Conclusions This SLR highlights the importance of early referral for patients with EA and confirms that RF and mainly ACPAs as well as a search for structural X-rays changes may help in the diagnosis and prognosis of patients with EA. PMID:28155923
Firth, J; Snowden, N; Ledingham, J; Rivett, A; Galloway, J; Dennison, EM; MacPhie, E; Ide, Z; Rowe, I; Kandala, N; Jameson, K
The first national audit for rheumatoid and early inflammatory arthritis has benchmarked care for the first three months of follow up activity from first presentation to a rheumatology service. Access to care, management of early RA and support for self care were measured against NICE quality standards and impact of early arthritis and experience of care were measured using patient reported outcome and experience measures. The results demonstrate delays in referral and accessing specialist care and the need for service improvement in treating to target, suppression of high levels of disease activity and support for self-care. Improvements in patient -reported outcomes within three months and high levels of overall satisfaction were reported but these results were affected by low response rates. Here we present a summary of the national data from the audit and discuss the implications for nursing practice. PMID:27281595
Forslind, K; Ahlmen, M; Eberhardt, K; Hafstrom, I; Svensson, B
Objective: To investigate the role of anti-cyclic citrullinated peptide antibody (anti-CCP) for the prediction of radiological outcome in patients with early rheumatoid arthritis. Methods: Anti-CCP was assessed at baseline in 379 patients with early rheumatoid arthritis (disease duration <1 year). Radiological joint damage and progression were assessed by Larsen score after two years of follow up (end point) and used as outcome variables. The prognostic value of anti-CCP and other demographic and disease related baseline variables were assessed by univariate and multivariate analyses, including calculation of odds ratios (OR), predictive values, and multiple logistic regression models. Results: The presence of anti-CCP was associated with significantly higher Larsen score both at baseline and at end point. Univariate predictor analysis showed that anti-CCP had the highest significant OR for radiological joint damage and progression after baseline Larsen score, followed by rheumatoid factor, erythrocyte sedimentation rate (ESR), C reactive protein, age, smoking status, and sex. In stepwise multiple regression analyses, baseline Larsen score, anti-CCP, and ESR were selected as significant independent predictors of the radiological outcomes. Conclusions: There is good evidence for an association of anti-CCP with radiological joint changes in rheumatoid arthritis. Anti-CCP is an independent predictor of radiological damage and progression. Though prediction in early rheumatoid arthritis is still far from perfect, the use of anti-CCP in clinical practice should make it easier for rheumatologists to reach judicious treatment decisions. PMID:15308518
Patients lacking classical poor prognostic markers might also benefit from a step-down glucocorticoid bridging scheme in early rheumatoid arthritis: week 16 results from the randomized multicenter CareRA trial.
Verschueren, Patrick; De Cock, Diederik; Corluy, Luk; Joos, Rik; Langenaken, Christine; Taelman, Veerle; Raeman, Frank; Ravelingien, Isabelle; Vandevyvere, Klaas; Lenaerts, Jan; Geens, Elke; Geusens, Piet; Vanhoof, Johan; Durnez, Anne; Remans, Jan; Vander Cruyssen, Bert; Van Essche, Els; Sileghem, An; De Brabanter, Griet; Joly, Johan; Van der Elst, Kristien; Meyfroidt, Sabrina; Westhovens, Rene
Considering a lack of efficacy data in patients with early rheumatoid arthritis (eRA) presenting without classical markers of poor prognosis, we compared methotrexate (MTX) with or without step-down glucocorticoids in the CareRA trial. Disease-modifying antirheumatic drug-naïve patients with eRA were stratified into a low-risk group based on prognostic markers that included non-erosiveness, anti-citrullinated protein antibodies and rheumatoid factor negativity and low disease activity (Disease Activity Score in 28 joints based on C-reactive protein (DAS28(CRP)) ≤3.2). Patients were randomized to 15 mg of MTX weekly (MTX with tight step-up (MTX-TSU)) or 15 mg of MTX weekly with prednisone bridging, starting at 30 mg and tapered to 5 mg daily from week 6 (COmbinatie therapie bij Reumatoïde Artritis (COBRA Slim)). A TSU approach was applied. Outcomes assessed were DAS28(CRP)-determined remission, cumulative disease activity, Health Assessment Questionnaire (HAQ) scores and adverse events (AEs) after 16 treatment weeks. We analyzed 43 COBRA Slim and 47 MTX-TSU patients and found that 65.1% in the COBRA Slim group and 46.8% in the MTX-TSU group reached remission (P = 0.081). Mean ± standard deviation area under the curve values of DAS28(CRP) were 13.84 ± 4.58 and 11.18 ± 4.25 for the MTX-TSU and COBRA Slim patients, respectively (P = 0.006). More COBRA Slim patients had an HAQ score of 0 (51.2% versus 23.4%, P = 0.006) at week 16. Therapy-related AEs between groups did not differ. In patients with low-risk eRA, MTX with step-down glucocorticoid bridging seems more efficacious than MTX step-up monotherapy, with a comparable number of AEs observed over the first 16 treatment weeks. EU Clinical Trials Register Identifier: EudraCT number 2008-007225-39 . Registered 5 November 2008.
Yilmaz, Sedat; Simsek, Ismail
Tocilizumab is a fully humanized monoclonal antibody against interleukin-6 receptors that was approved for the treatment of patients with rheumatoid arthritis (RA). Several lines of evidence, obtained both from conventional disease-modifying anti-rheumatic drugs (DMARDs) and tumor necrosis factor (TNF) inhibitors, have supported the concept of “window of opportunity” as showing that these therapies consistently work better in early disease as compared to established RA. This review addresses the question of whether a window of opportunity gained with conventional DMARDs and TNF inhibitors can also be achieved with tocilizumab. To this end, data regarding the use of tocilizumab in early RA patients are summarized. Currently available data suggest that the earlier the treatment with tocilizumab, the better the clinical outcome can be, which may have implications for various aspects of RA treatment strategies. PMID:24179334
Dāvidsone, Zane; Eglīte, Jeļena; Lazareva, Arina; Dzelzīte, Sarmīte; Šantere, Ruta; Bērziņa, Dace; Staņēviča, Valda
Temporomandibular joint (TMJ) arthritis is seen very often (38-87 %) in children with juvenile idiopathic arthritis (JIA). With contrast enhanced magnetic resonance imaging (MRI) we can detect more cases of TMJ arthritis than ever before. Previous studies show that HLA II class alleles may have protective or risk importance in JIA subtypes. Our objective is to identify HLA II class alleles of risk and protection in JIA patients with TMJ arthritis. During the period from 2010 to 2015 MRI for TMJ was performed in 85 JIA patients who were genotyped for HLA- DRB1; DQB1 and DQA1 using RT-PCR with sequence-specific primers. As a control group, data of 100 individuals were taken from the genetic bank of RSU Joint Laboratory of Clinical Immunology and Immunogenetics. Associations of DRB1; DQB1; DQA1 alleles in patients were examined individually using the χ (2) test. P-value (<0.05) and odds ratio were calculated using EPI INFO 6.0 software. Out of 85 JIA patients with mean age of 13.7 ± 3.0 years (range 6.9-17.9 years), 59 (69 %) were girls and 26 (31 %) were boys. The mean duration of the disease was 3.07 ± 2.35 years (range 0.2-11.0 year). JIA subtypes were as follows: seronegative polyarthritis 51 (60 %), seropositive polyarthritis 6(7 %), oligoarthritis extended 7(8 %), oligoarthritis persistent 2 (2 %) arthritis with enthesitis 14 (17 %), undifferentiated 3 (4 %) and 2 (2 %) systemic arthritis. Two groups where separated after TMJ MRI exam: first with at least two signs of active inflammation and/or any structural damage (n = 62); second with no pathologic signs or with slight contrast enhancement (n = 23). We discovered that there are risk alleles that are found in all JIA patient's groups (MRI positive and negative groups) versus controls such as DRB1*07:01, DQB1*03:03; DQB1*05:01. Also some protective alleles as DRB1*18:01, DQB1*06:02-8 were found in overall JIA group. Alleles DRB1*12:01, DQB1*03:01; DQA1*05:01 were found to be
Barra, Lillian J; Pope, Janet E; Hitchon, Carol; Boire, Gilles; Schieir, Orit; Lin, Daming; Thorne, Carter J; Tin, Diane; Keystone, Edward C; Haraoui, Boulos; Jamal, Shahin; Bykerk, Vivian P
. RA is associated with an increased risk of cardiovascular events (CVEs). The objective was to estimate independent effects of RA autoantibodies on the incident CVEs in patients with early RA. Patients were enrolled in the Canadian Early Inflammatory Arthritis Cohort, a prospective multicentre inception cohort. Incident CVEs, including acute coronary syndromes and cerebrovascular events, were self-reported by the patient and partially validated by medical chart review. Seropositive status was defined as either RF or ACPA positive. Multivariable Cox proportional hazards survival analysis was used to estimate the effects of seropositive status on incident CVEs, controlling for RA clinical variables and traditional cardiovascular risk factors. . A total of 2626 patients were included: the mean symptom duration at diagnosis was 6.3 months ( s . d . 4.6), the mean age was 53 years ( s . d . 15), 72% were female and 86% met classification criteria for RA. Forty-six incident CVEs occurred over 6483 person-years [incidence rate 7.1/1000 person-years (95% confidence interval 5.3, 9.4)]. The CVE rate did not differ in seropositive vs seronegative subjects and seropositivity was not associated with incident CVEs in multivariable Cox regression models. Baseline covariates independently associated with incident CVEs were older age, a history of hypertension and a longer duration of RA symptoms prior to diagnosis. The rate of CVEs early in the course of inflammatory arthritis was low; however, delays in the diagnosis of arthritis increased the rate of CVEs. Hypertension was the strongest independent risk factor for CVEs. Results support early aggressive management of RA disease activity and co-morbidities to prevent severe complications.
Çukurova, Selçuk; Pamuk, Ömer Nuri; Ünlü, Ercüment; Pamuk, Gülsüm Emel; Çakir, Necati
We evaluated the incidence of subclinical atherosclerosis and associated factors in our gouty arthritis patients. We included 55 gouty arthritis patients diagnosed at our center within the last 4 years. The control group included 41 patients with rheumatoid arthritis (RA) and 34 patients with asymptomatic hyperuricemia (AHU). Atherosclerotic risk factors were determined in all subjects. Carotid intima-media thickness (IMT) and the presence of plaques were evaluated by B-mode ultrasonography. The carotid IMT in gouty arthritis patients (0.730 ± 0.19) was significantly higher than in AHU subjects (0.616 ± 0.12) (P = 0.004) and tended to be higher than the RA group (0.669 ± 0.17) (P = 0.1). Atheromatous plaques were significantly more frequent in gouty arthritis patients (16 cases, 29.1%) than in RA patients (5 cases, 12.2%) and AHU subjects (3 cases, 8.8%) (P values, 0.05 and 0.023). Gout patients with plaques were older (P = 0.006) and tended to have tophi more frequently (P = 0.06). Logistic regression analysis showed that age (OR: 1.3, 95% CI: 1.02-1.54) and the presence of tophi (OR: 12.5, 95% CI: 1.2-140) were independent risk factors for the presence of plaques. Gouty arthritis bears a higher risk of atherosclerosis than both RA and AHU.
Hashimoto, Motomu; Yamazaki, Toru; Hamaguchi, Masahide; Morimoto, Takeshi; Yamori, Masashi; Asai, Keita; Isobe, Yu; Furu, Moritoshi; Ito, Hiromu; Fujii, Takao; Terao, Chikashi; Mori, Masato; Matsuo, Takashi; Yoshitomi, Hiroyuki; Yamamoto, Keiichi; Yamamoto, Wataru; Bessho, Kazuhisa; Mimori, Tsuneyo
Purpose To determine whether the presence of periodontitis (PD) and Porphyromonas gingivalis (Pg) in the subgingival biofilm associates with the development of rheumatoid arthritis (RA) in treatment naïve preclinical stage of arthritis patients. Methods We conducted a prospective cohort study of 72 consecutive patients with arthralgia who had never been treated with any anti-rheumatic drugs or glucocorticoids. Periodontal status at baseline was assessed by dentists. PD was defined stringently by the maximal probing depth≧4 mm, or by the classification by the 5th European Workshop in Periodontology (EWP) in 2005 using attachment loss. Up to eight plaque samples were obtained from each patient and the presence of Pg was determined by Taqman PCR. The patients were followed up for 2 years and introduction rate of methotrexate (MTX) treatment on the diagnosis of RA was compared in patients with or without PD or Pg. Results Patients with PD (probing depth≧4mm) had higher arthritis activity (p = 0.02) and higher risk for future introduction of MTX treatment on the diagnosis of RA during the follow up than patients without PD (Hazard ratio 2.68, p = 0.03). Arthritis activity and risk for MTX introduction increased with the severity of PD assessed by EWP, although not statistically significant. On the other hand, presence of Pg was not associated with arthritis activity (p = 0.72) or the risk for MTX introduction (p = 0.45). Conclusion In treatment naïve arthralgia patients, PD, but not the presence of Pg, associates with arthritis activity and future requirement of MTX treatment on the diagnosis of RA. PMID:25849461
Stolk, J N; Boerbooms, A M; De Abreu, R A; Kerstens, P J; de Koning, D G; de Graaf, R; Mulder, J; van de Putte, L B
OBJECTIVE: Purine enzyme activities may predict the effectiveness of azathioprine treatment and be associated with increased deaths from infectious diseases. In rheumatoid arthritis, patients show variable responses to azathioprine and a higher percentage of death is caused by infections. The aim of the study was to investigate possible rheumatoid arthritis associated abnormalities of purine enzyme activities by measuring several of these enzymes in patients with recent onset rheumatoid arthritis before treatment with disease modifying antirheumatic drugs or prednisone. METHODS: 23 patients with recent onset rheumatoid arthritis and 28 healthy controls were studied. Activities of the enzymes 5'-nucleotidase, purine nucleoside phosphorylase (PNP), hypoxanthine guanine phosphoribosyltransferase (HGPRT), and thiopurine methyltransferase (TPMT) were measured. Assessment of disease activity and blood sampling for routine measurements and HLA typing were done simultaneously. RESULTS: Purine enzyme activities did not differ between patients and healthy controls. Enzyme activities had no significant relations with indices of disease activity or rheumatoid factor titre or with the rheumatoid arthritis associated HLA types. Activity of 5'nucleotidase decreased with age (P < or = 0.05) and was lower by about 27% (P = 0.007) in males than in females. CONCLUSIONS: In rheumatoid arthritis patients, neither the variability in azathioprine effectiveness nor the increased death rate from infections can be explained by pre-existing abnormalities in the activities of the purine enzymes 5'-nucleotidase, PNP, HGPRT, or TPMT at an early stage of the disease, before disease modifying antirheumatic drugs or prednisone treatment. Besides adjustment for age, results of studies involving purine 5' nucleotidase activity should also be adjusted for sex. PMID:8984938
Abdelsalam, Safa K; Hashim, Nada T; Elsalamabi, Emitithal M; Gismalla, Bakri G
Few studies have investigated the periodontal condition among Rheumatoid arthritis in Sudan. The present study described the periodontal condition among Sudanese patients suffering from rheumatoid arthritis and to compare them with those of non-rheumatic subjects. A group of eighty rheumatoid arthritis patients was selected from Patient's Rheumatoid Clinics in Khartoum State during the period of January to May 2010. A control group of eighty patients with the same age and gender was selected for the study. Both Rheumatoid arthritis patients and the control group were examined for their plaque index, gingival index, and clinical attachment loss. The results revealed that there were no significant differences in plaque and gingival index among study and control groups, with mean plaque index of (1.25 ± 0.4) for patients and (1.17 ± 0.28) for the control group (p-value is 0.3597). The mean gingival index was (1.2 ± 0.24) for the patients and (1.2 ± 0.33) for the control (p = is 0.3049). The results showed statistically significant differences in clinical attachment loss between study and control groups, with mean clinical attachment loss of (1.03 ± 0.95) for the study group and (0.56 ± 0.63) for the control group (p = 0.0002). The study revealed that no association exists between the type of drug used to treat rheumatoid arthritis (NSAIDs & DMARDs) and the periodontal parameters (plaque index, gingival index, and clinical attachment loss). A significant relationship between periodontal disease and Rheumatoid Arthritis does exist, but no difference between plaque and gingival index has been detected among study and control groups.
Durham, Catherine O; Fowler, Terri; Donato, AnneMarie; Smith, Whitney; Jensen, Elizabeth
Rheumatoid arthritis (RA) is one of the most common inflammatory conditions in the United States affecting approximately 1 million adults. This article briefly reviews the evidence-based diagnosis of RA, mainstays of treatment to prevent joint destruction, and pain management.
De Cock, Diederik; Van der Elst, Kristien; Meyfroidt, Sabrina; Verschueren, Patrick; Westhovens, René
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune condition traditionally viewed as a severe destructive disease affecting physical health and global wellbeing. The treatment strategies for RA have changed in the last decades from mainly symptomatic towards a more vigorous and targeted approach. Reviewing recent literature enhanced by own expertise and research, a case is made for starting early with an intensive combination treatment with glucocorticoids, followed by a treat to target approach in a tight control setting. Implementation issues that need to be addressed to make optimal use of the 'window of opportunity' are highlighted. There is strong evidence in favor of traditional synthetic disease-modifying anti-rheumatic drugs (DMARDs) combined with a remission induction scheme of glucocorticoids to achieve adequate efficacy in controlling early rheumatoid arthritis with good safety and feasibility in daily clinical practice. Furthermore, the most optimal RA treatment should address not only the physician-oriented clinical disease outcomes but also the patient perspective. There is still a need for working on improving implementation of this approach in daily practice in order to provide optimal treatment benefit to more patients.
Sudoł-Szopińska, Iwona; Schueller-Weidekamm, Claudia; Plagou, Athena; Teh, James
Ultrasound is currently performed in everyday rheumatologic practice. It is used for early diagnosis, to monitor treatment results, and to diagnose remission. The spectrum of pathologies seen in arthritis with ultrasound includes early inflammatory features and associated complications. This article discusses the spectrum of ultrasound features of arthritides seen in rheumatoid arthritis and other connective tissue diseases in adults, such as Sjögren syndrome, lupus erythematosus, dermatomyositis, polymyositis, and juvenile idiopathic arthritis. Ultrasound findings in spondyloarthritis, osteoarthritis, and crystal-induced diseases are presented. Ultrasound-guided interventions in patients with arthritis are listed, and the advantages and disadvantages of ultrasound are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.
Lasry, S; Simon, J; Marais, A; Pouchot, J; Vinceneux, P; Boussougant, Y
We report on the first case of documented Helicobacter cinaedi septic arthritis in an immunocompetent heterosexual young man. The patient presented no identified risk factor except for contact with animals that have been incriminated as a possible source of infection, particularly for these patients. Despite prolonged bacteremia, the response to long-term therapy with ciprofloxacin and rifampin was excellent.
... joints Infection, most often by bacteria or virus Crystals such as uric acid or calcium pyrophosphate dihydrate ... common types of inflammatory arthritis include: Ankylosing ... calcium pyrophosphate deposition disease Juvenile rheumatoid ...
Bedoya, María Eugenia; Ceccato, Federico; Paira, Sergio
We describe the case of a 51-year-old woman with a seropositive, erosive, and non-nodular rheumatoid arthritis of 15 year of evolution. The patient had poor compliance with medical visits and treatment. She came to the clinic with persistent pancytopenia and spleen and liver enlargement. Liver and bone marrow biopsies were carried out and amyloidosis, neoplasias and infections were ruled out. We discuss the differential diagnosis of pancytopenia and spleen and liver enlargement in a long-standing rheumatoid arthritis patient. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.
Blinova, E A; Zinnatova, E V; Barkovskaya, M Sh; Borisov, V I; Sizikov, A E; Kozhevnikov, V S; Rubtsov, N B; Kozlov, V A
We analyzed telomere length of individual chromosomes in peripheral blood lymphocytes of healthy individuals and patients with rheumatoid arthritis. Quantitative fluorescent in situ hybridization and subsequent computer analysis of metaphase chromosomes showed that distribution of telomere length on individual chromosomes is different under normal and pathological conditions. Patients with rheumatoid arthritis had significantly shorter chromosome 4p telomeres, which can be essential for pathogenesis of this multifactorial disease. Additionally, disease activity inversely correlated with telomere length on chromosome 10p carrying genes involved in T cell differentiation and proliferation.
Schäd, Susanne G; Kraus, Andrea; Haubitz, Imme; Trcka, Jiri; Hamm, Henning; Girschick, Hermann J
Pseudoporphyria (PP) is characterized by skin fragility, blistering and scarring in sun-exposed skin areas without abnormalities in porphyrin metabolism. The phenylpropionic acid derivative group of nonsteroidal anti-inflammatory drugs, especially naproxen, is known to cause PP. Naproxen is currently one of the most prescribed drugs in the therapy of juvenile idiopathic arthritis (JIA). The prevalence of PP was determined in a 9-year retrospective study of children with JIA and associated diseases. In addition, we prospectively studied the incidence of PP in 196 patients (127 girls and 69 boys) with JIA and associated diseases treated with naproxen from July 2001 to March 2002. We compared these data with those from a matched control group with JIA and associated diseases not treated with naproxen in order to identify risk factors for development of PP. The incidence of PP in the group of children taking naproxen was 11.4%. PP was particularly frequent in children with the early-onset pauciarticular subtype of JIA (mean age 4.5 years). PP was associated with signs of disease activity, such as reduced haemoglobin (<11.75 g/dl), and increased leucocyte counts (>10,400/μl) and erythocyte sedimentation rate (>26 mm/hour). Comedications, especially chloroquine intake, appeared to be additional risk factors. The mean duration of naproxen therapy before the onset of PP was 18.1 months, and most children with PP developed their lesions within the first 2 years of naproxen treatment. JIA disease activity seems to be a confounding factor for PP. In particular, patients with early-onset pauciarticular JIA patients who have significant inflammation appear to be prone to developing PP upon treatment with naproxen. PMID:17266758
Zabek, Adam; Swierkot, Jerzy; Malak, Anna; Zawadzka, Iga; Deja, Stanisław; Bogunia-Kubik, Katarzyna; Mlynarz, Piotr
Rheumatoid arthritis is a chronic autoimmune-based inflammatory disease that leads to progressive joint degeneration, disability, and an increased risk of cardiovascular complications, which is the main cause of mortality in this population of patients. Although several biomarkers are routinely used in the management of rheumatoid arthritis, there is a high demand for novel biomarkers to further improve the early diagnosis of rheumatoid arthritis, stratification of patients, and the prediction of a better response to a specific therapy. In this study, the metabolomics approach was used to provide relevant biomarkers to improve diagnostic accuracy, define prognosis and predict and monitor treatment efficacy. The results indicated that twelve metabolites were important for the discrimination of healthy control and rheumatoid arthritis. Notably, valine, isoleucine, lactate, alanine, creatinine, GPC APC and histidine relative levels were lower in rheumatoid arthritis, whereas 3-hydroxyisobutyrate, acetate, NAC, acetoacetate and acetone relative levels were higher. Simultaneously, the analysis of the concentration of metabolites in rheumatoid arthritis and 3 months after induction treatment revealed that L1, 3-hydroxyisobutyrate, lysine, L5, acetoacetate, creatine, GPC+APC, histidine and phenylalanine were elevated in RA, whereas leucine, acetate, betaine and formate were lower. Additionally, metabolomics tools were employed to discriminate between patients with different IL-17A genotypes. Metabolomics may provide relevant biomarkers to improve diagnostic accuracy, define prognosis and predict and monitor treatment efficacy in rheumatoid arthritis.
George, Michael David; Cardenas, Ana Maria; Birnbaum, Belinda K; Gluckman, Stephen J
Mycoplasmas, including Ureaplasma and Mycoplasma species, are uncommon but important causes of septic arthritis, especially affecting immunosuppressed patients. Many of the reported cases have been associated with congenital immunodeficiency disorders, especially hypogammaglobulinemia. Mycoplasmas are difficult to grow in the laboratory, and these infections may be underdiagnosed using culture techniques. We report a case of a 21-year-old woman with juvenile idiopathic arthritis and hip arthroplasties treated with rituximab and adalimumab who developed urogenital infections and soft tissue abscesses followed by knee arthritis with negative routine cultures. Ureaplasma species was identified from synovial fluid on 2 separate occasions using a broad-range 16S ribosomal RNA gene polymerase chain reaction. Azithromycin led to rapid improvement in symptoms, but after completion of therapy, involvement of the hip prosthesis became apparent, and again, 16S rRNA gene polymerase chain reaction was positive for Ureaplasma species. The literature is reviewed with a discussion of risk factors for Mycoplasma septic arthritis, clinical presentation, methods of diagnosis, and treatment.
Pfeifer, Emily C; Crowson, Cynthia S; Amin, Shreyasee; Gabriel, Sherine E; Matteson, Eric L
Objective: Early menopause is associated with an increased risk for developing rheumatoid arthritis (RA). The risk for cardiovascular disease (CVD) in women increases following menopause. Since RA is associated with an increased risk of CVD, this study was undertaken to determine if early menopause affects the risk of developing CVD in women with RA. Methods: A population-based inception cohort of 600 women with RA who fulfilled 1987 ACR criteria for RA between 1955 and 2007 and were age ≥ 45 years at diagnosis was assembled and followed. Age at menopause and duration of hormone replacement therapy (HRT), along with occurrence of CVD was ascertained by review of medical records. Cox proportional hazard models compared women who underwent early menopause (natural or artificial menopause at age ≤ 45 years) to those within the cohort who did not undergo early menopause. Results: Of 600 women, 79 exprienced early menopause. Women who underwent early menopause were at significantly higher risk for developing CVD when compared to women who did not (hazard ratio (HR): 1.56; 95% CI: 1.08-2.26). Conclusion: The risk of CVD in women with RA was higher in those who experience early menopause, and like other known risk factors should increase clinician concern for development of CVD in these patients. PMID:24882842
Adizie, T; Moots, R J; Hodkinson, B; French, N; Adebajo, A O
Musculoskeletal manifestations of the human immunodeficiency virus (HIV) have been described since the outset of the global HIV epidemic. Articular syndromes that have been described in association with HIV include HIV-associated arthropathy, seronegative spondyloarthropathies (SPA) (reactive arthritis, psoriatic arthritis (PsA) and undifferentiated SPA), rheumatoid arthritis (RA) and painful articular syndrome. We carried out a computer-assisted search of PubMed for the medical literature from January 1981 to January 2015 using the keywords HIV, acquired immune-deficiency syndrome, rheumatic manifestations, arthritis, spondyloarthropathy, anti-TNF and disease modifying antirheumatic drugs. Only English language literature was included and only studies involving adult human subjects were assessed. There are challenges in the management of inflammatory arthritis in patients who are HIV-positive, including difficulties in the assessment of disease activity and limited information on the safety of immunosuppressive drugs in these individuals. This review focuses on the clinical characteristics of the inflammatory articular syndromes that have been described in association with HIV infection and discusses the therapeutic options for these patients.
Resorlu, Hatice; Sahin, Basak; Ertekin, Hulya; Bilim, Serhad; Savas, Yılmaz
Aim To investigate marital adjustment in patients with rheumatoid arthritis and factors affecting this. Methods A total of 32 patients diagnosed with Steinbrocker class 1-2 rheumatoid arthritis and 32 healthy individuals from a similar age group were included. Sociodemographic characteristics, the Beck Depression Inventory (BDI), short-form 36(SF-36) and the dyadic adjustment scale (DAS) were evaluated in both groups. A visual analogue scale (VAS), the disease activity score 28(DAS28) and a health assessment questionnaire (HAQ) were also investigated in the patient group. Results Mean ages were 46.5±9.2 years in the patient group and 47.7±8.1 in the control group (p=0.5). No significant difference was determined between the two groups in terms of sociodemographic characteristics. No statistically significant correlation was observed between erythrocyte sedimentation rate (ESR), patient and physician global VAS, DAS28, HAQ and morning stiffness and DAS total score. Comparison of DAS subunits revealed a significant difference in dyadic satisfaction and affectional expression in the patient and control groups (p=0.046 and p=0.037). A statistically significant negative correlation was observed between duration of the disease and marital adjustment (p=0.01;r= -0.58). Conclusion Due to its progressive and prolonged course rheumatoid arthritis can also affect individuals' social relationships besides restricted daily living activities. Activation of rheumatoid arthritis did not affect marital adjustment in this study, but adjustment decreased with duration of the disease.
The Relationship between Personality, Supportive Transactions and Support Satisfaction, and Mental Health of Patients with Early Rheumatoid Arthritis. Results from the Dutch Part of the Euridiss Study
Suurmeijer, Th. P. B. M.; Van Sonderen, F. L. P.; Krol, B.; Doeglas, D. M.; Van Den Heuvel, W. J. A.; Sanderman, R.
The relationships between two personality characteristics (neuroticism, extraversion), three types of supportive transactions (emotional support, social companionship, instrumental support) and satisfaction with these transactions, and two aspects of mental health (feelings of anxiety and depressive mood) were studied among 280 patients with early…
The Relationship between Personality, Supportive Transactions and Support Satisfaction, and Mental Health of Patients with Early Rheumatoid Arthritis. Results from the Dutch Part of the Euridiss Study
Suurmeijer, Th. P. B. M.; Van Sonderen, F. L. P.; Krol, B.; Doeglas, D. M.; Van Den Heuvel, W. J. A.; Sanderman, R.
The relationships between two personality characteristics (neuroticism, extraversion), three types of supportive transactions (emotional support, social companionship, instrumental support) and satisfaction with these transactions, and two aspects of mental health (feelings of anxiety and depressive mood) were studied among 280 patients with early…
Gilbert, M S; Aledort, L M; Seremetis, S; Needleman, B; Oloumi, G; Forster, A
Before 1983, septic arthritis was rare in patients with hemophilia. With the advent of human immunodeficiency virus infection in the hemophilia population, many centers noted an increasing incidence of patients with septic arthritis. Fifteen septic joints in 10 patients with severe hemophilia were documented. Eight patients were human immunodeficiency virus positive, 1 was human immunodeficiency virus negative, and 1 was not tested. The diagnosis was delayed in 5 patients because the symptoms are similar to an acute hemarthrosis. An elevated temperature was common. The white blood cell count was elevated in only 1/3 of the infections, being modified by human immunodeficiency virus infection. Associated risk factors included infected angioaccess catheters (2), pneumonia (2), and generalized sepsis (1). All but 1 joint responded to appropriate antibiotics and either repeated aspiration or arthrotomy. However, 6 patients died of acquired immunodeficiency syndrome from 2 to 109 months after infection. Three patients are alive 29, 86, and 96 months, respectively, after infection.
Turina, Maureen C; Yeremenko, Nataliya; van Gaalen, Floris; van Oosterhout, Maikel; Berg, Inger J; Ramonda, Ramona; Lebre, Cristina (M C); Landewé, Robert; Baeten, Dominique
Introduction Decreasing the diagnostic delay in axial spondyloarthritis (axSpA) remains a major challenge. Here, we assessed the value of serum inflammatory biomarkers to distinguish early axSpA from other pathologies in a large cohort of patients referred with early back pain. Methods Serum c reactive protein (CRP), erythrocyte sedimentation rate (ESR) and calprotectin were determined in the SPondyloArthritis Caught Early (SPACE) cohort (n=310), an early back pain inception cohort. Additionally, explorative serum biomarkers derived from the literature (interleukin-27 (IL-27), human β-defensin-2 (hBD-2) and lipcolin-2 (LCN-2)) were determined by ELISA in full-blown patients with ankylosing spondylitis (AS) (n=21) and healthy controls (n=20). Results Serum CRP and ESR levels were not elevated in early axSpA versus ‘control’ back pain patients. Serum calprotectin was elevated in early axSpA versus controls (p=0.01) but failed to identify early axSpA at the individual level (positive predictive value of 38.7%). As to explorative biomarkers, serum levels of IL-27 were not detectable, and hBD-2 and LCN-2 serum levels were not elevated in full-blown AS versus healthy controls (p=0.572, p=0.562, respectively). Therefore, these markers were not further determined in the SPACE cohort. Conclusions None of the candidate serum inflammatory markers were useful as diagnostic markers in the early phase of axSpA. PMID:28123777
Straaton, K.V.; Lopez-Mendez, A.; Alarcon, G.S. )
We describe 3 patients with rheumatoid arthritis who presented with diffuse pain, swelling, and erythema of the distal aspect of the lower extremity, suggestive of either cellulitis or thrombophlebitis, but were found to have insufficiency fractures of the distal tibia. The value of technetium-99m diphosphonate bone scintigraphy in the early recognition of these fractures and a possible explanation for the associated inflammatory symptoms are discussed.
Pohjankoski, Heini; Kautiainen, Hannu; Kotaniemi, Kaisu; Korppi, Matti; Savolainen, Anneli
To evaluate the occurrence of autoimmune diseases in first-degree relatives of children with juvenile idiopathic arthritis (JIA) and to compare the figures with published population data. Families of the 362 children with recently diagnosed JIA admitted to Rheumatism Foundation Hospital, Finland, from 1996 to 2001 were contacted by questionnaires regarding autoimmune diseases in family members. Data were collected on type 1 diabetes, coeliac disease, multiple sclerosis and chronic arthritis, consisting mainly of JIA, rheumatoid arthritis, spondyloarthropathy or psoriatic arthritis. In all, 21.4% of the 355 families with a patient with JIA had members with type 1 diabetes, coeliac disease, multiple sclerosis or chronic arthritis. Thirty-three mothers and 23 fathers had type 1 diabetes, coeliac disease, multiple sclerosis or chronic arthritis in 15.2% (95% CI 11.6-19.4) of the families, and 23 mothers and 15 fathers had chronic arthritis in 10.7% (95% CI 7.7-14.5) of the families. When compared with available research data, the prevalences of rheumatoid arthritis, spondyloarthropathy, psoriatic arthritis, paediatric type 1 diabetes and JIA (in siblings) were increased in JIA families. Coeliac disease was as prevalent as in the population. Autoimmune diseases cluster in families with a child with JIA. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.
Meyfroidt, S; van Hulst, L; De Cock, D; Van der Elst, K; Joly, J; Westhovens, R; Hulscher, M; Verschueren, P
Despite the availability and demonstrated effectiveness of intensive combination treatment strategies (ICTS) for early rheumatoid arthritis (RA), a discrepancy seems to exist between theoretical evidence and actual prescription in daily practice. The purpose of this study was to explore and identify the factors influencing the prescription of ICTS. This study involved rheumatologists and nurses participating in the Care for Rheumatoid Arthritis (CareRA) trial, a multicentre randomized controlled trial (RCT) comparing different ICTS for early RA with conventional disease-modifying anti-rheumatic drugs (DMARDs) plus step-down glucocorticoids (GCs). A qualitative study was carried out using individual semi-structured interviews. Each interview was recorded, transcribed literally, and analysed thematically. In addition, observations at outpatient clinics were used to clarify the interpretation of the results. We interviewed 26 rheumatologists and six nurses and observed five outpatient visits. Identified facilitators included available scientific evidence, personal faith in treatment strategy, staff support, and low treatment costs. Rheumatologists had no doubts about the value of methotrexate (MTX) but some questioned the value of combination strategy, others the effectiveness and/or the dosage of individual compounds. Additional barriers for prescribing ICTS included need for patient education, fear for patients' preconceptions, concerns about applicability to the individual patient, difficulties with breaking routine, interference with organizational structures and processes, time constraints, and lack of financial support. A heterogeneous set of factors highlights the complexity of prescribing ICTS for early RA in daily clinical practice. Future improvement strategies should stimulate the facilitators while at the same time addressing the barriers. The generalizability of these findings to other health care systems needs further examination.
Treviño-González, José Luis; Villegas-González, Mario Jesús; Muñoz-Maldonado, Gerardo Enrique; Montero-Cantu, Carlos Alberto; Nava-Zavala, Arnulfo Hernán; Garza-Elizondo, Mario Alberto
The rheumatoid arthritis is a clinical entity capable to cause hearing impairment that can be diagnosed promptly with high frequencies audiometry. To detect subclinical sensorineural hearing loss in patients with rheumatoid arthritis. Cross-sectional study on patients with rheumatoid arthritis performing high frequency audiometry 125Hz to 16,000Hz and tympanometry. The results were correlated with markers of disease activity and response to therapy. High frequency audiometry was performed in 117 female patients aged from 19 to 65 years. Sensorineural hearing loss was observed at a sensitivity of pure tones from 125 to 8,000 Hz in 43.59%, a tone threshold of 10,000 to 16,000Hz in 94.02% patients in the right ear and in 95.73% in the left ear. Hearing was normal in 8 (6.84%) patients. Hearing loss was observed in 109 (93.16%), and was asymmetric in 36 (30.77%), symmetric in 73 (62.37%), bilateral in 107 (91.45%), unilateral in 2 (1.71%), and no conduction and/or mixed hearing loss was encountered. Eight (6.83%) patients presented vertigo, 24 (20.51%) tinnitus. Tympanogram type A presented in 88.90% in the right ear and 91.46% in the left ear, with 5.98 to 10.25% type As. Stapedius reflex was present in 75.3 to 85.2%. Speech discrimination in the left ear was significantly different (p = 0.02)in the group older than 50 years. No association was found regarding markers of disease activity, but there was an association with the onset of rheumatoid arthritis disease. Patients with rheumatoid arthritis had a high prevalence of sensorineural hearing loss for high and very high frequencies. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.
Rapoport, I E; Luchikhina, E L; Pogozheva, E Iu; Smirnov, A V; Karateev, D E
To provide the qualitative and quantitative characteristics of changes revealed by the data of magnetic resonance imaging (MRI) of the hand and by those of X-ray study of the hand and foot in patients with early rheumatoid arthritis (ERA). The study enrolled 110 patients (90 females, 20 males; age 49.6 +/- 12.2 years) examined in the framework of the RADICAL program at the Research Institute of Rheumatology, Russian Academy of Medical Sciences. The mean duration of the disease was 5.61 +/- 3.17 months. The diagnosis of rheumatoid arthritis was established by the 1987 ARA criteria in all the patients on primary standard examination comprising X-ray study of the hand and feet and evaluation by the modified Sharp method. MRI of the hand was performed in all the patients, by assessing the result by the OMERACT-RAMRIS procedure. Destructive changes (cysts and erosions) evidenced by X-ray study were found in the wrists, metacarpophalangeal articulations (MPA), and foot in 7.27, 8.2, and 13.64%, respectively. MRI revealed destructions in the wrist, MPA, and metacarpal bone base in 50, 60, and 16.36%, respectively. Overall, erosions could be seen on X-ray films and MRI scans in 20.91 and 67.27%, respectively (p < 0.0001). MRI revealed bone edema (osteitis) in 46.4% of the patients; there was no difference in the detection rate between the extremities. MRI synovitis was found in 99% of the patients, the right hand being significantly more commonly affected. Detailed characterization of the changes revealed by MRI and Xray was obtained in patients with ERA. MRI detected erosions significantly more frequently than did X-ray (p < 0.001), which confirms the high value of low-field MRI diagnosis on primary examination of patients with ERA and supports the opinion that the results of this study should be included into the diagnostic criteria of ERA.
Sbiti, Mohammed; Bouhamidi, Bahia; Louzi, Lhoussaine
Acute septic arthritis is rare. It is associated with poor prognosis in terms of mortality and morbidity. We report the case of a 61-year old patient with spontaneous Proteus mirabilis septic arthritis. He suffered from complicated diabetes associated with positive blood cultures and synovial fluid cultures. Patient's evolution was favorable thanks to early diagnosis and initiation of adequate antibiotic therapy. Proteus mirabilis septic arthritis is rare. On that basis we conducted a literature review of cases of Proteus mirabilis pyogenic arthritis to highlight the risk factors, pathogenesis, treatment and evolution of these diseases. Diagnosis is commonly based on microbiological analysis, early articular puncture biopsy is performed before the initiation of antibiotic treatment, direct examination, culture and antibiogram which are useful as guidance for antibiotic therapy. Septic arthritis is a diagnostic and therapeutic emergency; early management of this disease allows total healing without after-effects.
Wynes, Jacob; Harris, William; Hadfield, Robert A; Malay, D Scot
The clinical presentation of a monoarticular, red, hot, and swollen joint has many possible diagnoses, including septic arthritis, which is 1 of the most devastating. The morbidity associated with this pathologic process involves permanent joint damage and the potential for progression to systemic illness and, even, mortality. The common risk factors for joint sepsis include a history of rheumatoid arthritis, previous joint surgery, joint prosthesis, intravenous drug abuse, alcoholism, diabetes, previous intra-articular steroid use, and cutaneous ulceration. The diagnosis is primarily determined from the culture results after arthrocentesis and correlation with direct visualization, imaging, and various serologies, including synovial analysis. In the present report, a case of an insidious presentation of subtalar joint septic arthritis and its association with a unique patient presentation concomitant with primary immunodeficiency and culture-proven Myocplasma hominis infection is discussed. Septic arthritis has a predilection for the lower extremities and typically is isolated to the hip or knee, with less common involvement of the ankle or metatarsophalangeal joints. Owing to the uncommon nature of primary immunodeficiency disorders and the paucity of studies discussing their association with septic arthridites, we aimed to raise awareness of subtalar joint septic arthritis and to provide a brief overview of the pathogenesis as it presented in a 33-year-old male with X-linked hypogammaglobulinemia/agammaglobulinema. Copyright © 2013 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.
Gromnica-Ihle, E; Ostensen, M
The activity of a rheumatic disease can be influenced by pregnancy and puerperium. Prospective studies have shown an improvement in joint involvement in rheumatoid arthritis in two thirds to three quarters of pregnancies. After birth, an exacerbation is common. In spondylarthropathies there is no relevant change in disease activity. The fetal outcome is not impaired in patients with rheumatoid arthritis and inflammatory spondylarthropathies. Every pregnancy in women with a rheumatic disease should be considered as high-risk, and such pregnancies require close collaboration between rheumatologists and obstetricians.
Wynne, K M; Dieppe, P A; Scott, J; Huskisson, E C
A simple method is described which allows sequential monitoring of the endocytic activity of blood and synovial fluid cells from rheumatoid arthritis patients undergoing therapy with levamisole. Evidence of immediate (24 hours) and long-term (5-7 weeks) cellular phagocytic enhancement is presented. Images PMID:7259330
Woodbury, Anna; Jorgensen, James; Owens, Aaron; Henao-Martinez, Andres
Moraxella lacunata is a rare, usually commensal gram-negative rod most commonly associated with eye infections. We report a unique case of noniatrogenic M. lacunata bacteremia and septic knee arthritis in a patient with class III-IV lupus nephritis and speculate on the association between invasive Moraxella infection and renal impairment. PMID:19794049
Mekić, Mevludin; Ristić, Miomir
Rheumatoid arthritis is a chronic systematic inflammation illness characterized by progressive damage of joints. Treatment of rheumatoid arthritis is individual, programmed and complex and consists of general measures, application of adequate medication, physical procedures, balneotherapy and various surgical techniques as necessary. The objective of research is to show success of therapy in use of medication and other types of treatment for patients suffering from rheumatoid arthritis. The following were applied: non-steroid anti-inflammatory medications (NAIL), metotrexate, gold salts, corticosteroids, sulphasalzine, Chlorochin, cyclophosphamide and others. Metotrexate was often applied in our research and good results were achieved with it, but very good results were also achieved by combination of 2 or more immunodatulatory medications, including interarticular application of medication, physical, balneo and orthopedic therapy, as well as other alternative therapy. Success of therapy based on Richie index shows statistically significant improvement, meaning that there was movement from grade 3 and 4 into grades 1 and 2.
Younes, Mohamed; Korbaa, Wided; Moussa, Adnène; Zrour, Saoussen; Bejia, Ismail; Touzi, Mongi; Zakhama, Abdelfatteh; Bergaoui, Naceur
Secondary amyloidosis is a serious complication of rheumatoid arthritis (RA). Symptoms are late to occur, so that screening is in order, most notably in patients with long-standing RA. The objectives of our study were to determine the prevalence of subclinical amyloidosis in RA patients by abdominal fat aspiration biopsy (AFAB) and minor salivary gland biopsy (MSGB) and to identify factors associated with subclinical amyloidosis. We prospectively studied 107 consecutive patients with RA (94 women and 13 men) recruited between March 2005 and January 2006. Clinical and laboratory findings, imaging study results, and treatment were recorded for each patient. AFAB and MSGB were performed routinely. Amyloid deposits were identified by polarized light microscopy after Congo red staining. The prevalence of subclinical amyloidosis was 21.5% by AFAB and 3.7% by MSGB. Factors associated with subclinical amyloidosis were a longer time to diagnosis (P=0.03), extraarticular manifestations (P=0.019), proteinuria >0.3 g/24 h (P=0.024), and absence of methotrexate therapy (P=0.046). Subclinical amyloidosis was not associated with age, sex, RA duration, joint deformities, DAS28 score, Health Assessment Questionnaire score, Steinbrocker radiological stage, rheumatoid factor, erythrocyte sedimentation rate, C-reactive protein, creatinine, or hemoglobin. The prevalence of subclinical amyloidosis by AFAB is high (21.5%). AFAB is more sensitive than MSGB for detecting subclinical amyloidosis. A simple screening tool such as AFAB should be used, particularly in patients with risk factors. Subclinical amyloidosis requires close monitoring to ensure the early detection and treatment of symptomatic amyloidosis.
Turner-Stokes, L; Frank, A O
Urinary tract pathology may be no more common in patients with arthritis than among the general population, but its impact may be enhanced by disability. In this survey of 247 patients, as many as 38% of patients with rheumatoid arthritis (RA), 47% of patients with osteoarthritis (OA) and even 34% of patients with soft tissue rheumatism (STR) reported difficulty controlling their urine, confirming that incontinence is a widespread and often under-reported problem. More detailed enquiry in a sample of 90 patients with OA or RA did not suggest specific urinary tract pathology related to the underlying arthritis. Those who reported problems with urinary control were more disabled, and took longer to get to the toilet in their own environment than those without control problems. Twenty-seven per cent of patients felt that their problems would be solved by provision of a downstairs toilet. Timing of tasks performed by patients within their home is suggested as a method for assessing functional ability which encompasses both patient disability and environmental factors. PMID:1629846
Masson-Behar, Vanina; Jacquier, Hervé; Richette, Pascal; Ziza, Jean-Marc; Zeller, Valérie; Rioux, Christophe; Coustet, Baptiste; Dieudé, Philippe; Ottaviani, Sébastien
Arthritis secondary to invasive meningococcemia is rare and has been described as a direct result of bacteremia or as immunoallergic-type arthritis, related to the immune complex. Only a few case series have been reported.This multicenter study aimed to describe the clinical characteristics and therapeutic outcomes of arthritis secondary to meningococcal infection.We performed a 5-year retrospective study. We included all patients with inflammatory joint symptoms and proven meningococcal disease defined by the identification of Neisseria meningitidis in blood, cerebrospinal fluid, or synovial fluid. Septic arthritis was defined by the identification of N meningitidis in joint fluid. Immune-mediated arthritis was considered to be arthritis occurring after at least 1 day of invasive meningococcal disease without positive joint fluid culture.A total of 7 patients (5 males) with joint symptoms and meningococcal disease were identified. The clinical presentation was mainly oligoarticular and the knee was the most frequent joint site. Five patients had septic arthritis and 4 had immune-mediated arthritis; 2 had septic arthritis followed by immune-mediated arthritis. Immune-mediated arthritis occurred 3 to 7 days after meningococcal meningitis, and treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) led to improvement without complications.Physicians must be vigilant to the different clinical presentations in patients with arthritis associated with invasive meningococcal disease. If immune-mediated arthritis is suspected, NSAIDs are usually efficient.
Vázquez-Alonso, María Francisca; Viñas-Silva, Alberto
Scapholunate advance collapse (SLAC) and Scaphoid nonunion advance collapse (SNAC), are the two most common patterns of postraumatic wrist arthritis. SLAC wrist develops after attenuation, either traumatically or atraumatically, of the scapholunate ligament. Atraumatic causes of SLAC wrist include calcium pyrophosphate dehydrate deposition disease, reumathoid arthritis, neuropathic diseases, and b2-microglobulin asociated amyloid deposition diseases. On the other hand, SNAC wrist develops following a scahpoid fracture that has progressed to a nonunion. Both of these processes lead to abnormal joint kinematics, since the lunate is unrestrained by the distal scaphoid and, therefore, assumes an extended posture. Over time, this may result in Dorsal intercalated segment instability (DISI) deformity, which invariably progresses to degenerative arthritis of the radioescaphoid articulation, followed by carpal collapse and midcarpal arthritis. The purpose of this retrospective study is to evaluate the functional outcome and pain relief in SLAC/SNAC wrist, after four corner fusion. This study was made in 52 patients of the Hospital de Traumatología y Ortopedia Lomas Verdes, these patients undergone four corner fusion surgery, in a period january 2007 to december 2014. We used Quick Dash Questionary to evaluate functional outcome and pain relief in these patients.
Machado, Marina Amaral de Ávila; de Moura, Cristiano Soares; Ferré, Felipe; Bernatsky, Sasha; Rahme, Elham; Acurcio, Francisco de Assis
ABSTRACT OBJECTIVE To evaluate treatment persistence in patients with rheumatoid arthritis and ankylosing spondylitis who started therapies with disease-modifying antirheumatic drugs (DMARD) and tumor necrosis factor blockers (anti-TNF drugs). METHODS This retrospective cohort study from July 2008 to September 2013 evaluated therapy persistence, which is defined as the period between the start of treatment until it is discontinued, allowing for an interval of up to 30 days between the prescription end and the start of the next prescription. Odds ratio (OR) with 95% confidence intervals (95%CI) were calculated by logistic regression models to estimate the patients’ chances of persisting in their therapies after the first and after the two first years of follow-up. RESULTS The study included 11,642 patients with rheumatoid arthritis – 2,241 of these started on anti-TNF drugs (+/-DMARD) and 9,401 patients started on DMARD – and 1,251 patients with ankylosing spondylitis – 976 of them were started on anti-TNF drugs (+/-DMARD) and 275 were started on DMARD. In the first year of follow-up, 63.5% of the patients persisted in their therapies with anti-TNF drugs (+/-DMARD) and 54.1% remained using DMARD in the group with rheumatoid arthritis. In regards to ankylosing spondylitis, 79.0% of the subjects in anti-TNF (+/-DMARD) group and 41.1% of the subjects in the DMARD group persisted with their treatments. The OR (95%CI) for therapy persistence was 1.50 (1.34-1.67) for the anti-TNF (+/-DMARD) group as compared with the DMARD group in the first year for the patients with rheumatoid arthritis, and 2.33 (1.74-3.11) for the patients with ankylosing spondylitis. A similar trend was observed at the end of the second year. CONCLUSIONS A general trend of higher rates of therapy persistence with anti-TNF drugs (+/-DMARD) was observed as compared to DMARD in the study period. We observed higher persistence rates for anti-TNF drugs (+/-DMARD) in patients with ankylosing
Scuccimarri, R.; Azouz, E; Duffy, K.; Fassier, F.; Duffy, C.
Osteochondrodysplasias are a heterogeneous group of genetic skeletal dysplasias. Patients with these diseases commonly develop an early degenerative arthritis or osteoarthritis. Occasional observations of inflammatory arthritis have been made in this population but such observations are based on clinical grounds alone without confirmatory imaging studies. Four patients followed up in a paediatric rheumatology clinic with three different skeletal dysplasias, who had both clinical and radiological evidence of an inflammatory arthritis and coexistent degenerative arthritis, are described. PMID:11053062
Scuccimarri, R; Azouz, E M; Duffy, K N; Fassier, F; Duffy, C M
Osteochondrodysplasias are a heterogeneous group of genetic skeletal dysplasias. Patients with these diseases commonly develop an early degenerative arthritis or osteoarthritis. Occasional observations of inflammatory arthritis have been made in this population but such observations are based on clinical grounds alone without confirmatory imaging studies. Four patients followed up in a paediatric rheumatology clinic with three different skeletal dysplasias, who had both clinical and radiological evidence of an inflammatory arthritis and coexistent degenerative arthritis, are described.
Egeberg, A; Mallbris, L; Gislason, G; Hansen, P R; Mrowietz, U
Psoriasis and periodontitis are chronic inflammatory disorders with overlapping inflammatory pathways, but data on risk of periodontitis in psoriasis are scarce and a possible pathogenic link is poorly understood. We investigated the association between psoriasis and periodontitis in a nationwide cohort study. All Danish individuals aged ≥18 years between 1 January 1997 and 31 December 2011 (n = 5,470,428), including 54 210 and 6988 patients with mild and severe psoriasis, and 6428 with psoriatic arthritis, were linked through administrative registers. Incidence rate ratios (IRRs) were estimated by Poisson regression. Incidence rates of periodontitis per 10 000 person-years were 3.07 (3.03-3.12), 5.89 (1.07-6.84), 8.27 (5.50-12.45) and 11.12 (7.87-15.73) for the reference population, mild psoriasis, severe psoriasis and psoriatic arthritis respectively. Adjusted IRRs were (1.66; 1.43-1.94) for mild psoriasis, (2.24; 1.46-3.44) for severe psoriasis and (3.48; 2.46-4.92) for psoriatic arthritis. Similar results were found when a case-control design was applied. We found a significant psoriasis-associated increased risk of periodontitis, which was highest in patients with severe psoriasis and psoriatic arthritis. © 2016 European Academy of Dermatology and Venereology.
Szady, Paulina; Bączyk, Grażyna; Kozłowska, Katarzyna
Rheumatoid arthritis (RA) is a systemic disease of connective tissue characterised by chronic course with periods of exacerbation and remission. Even in the early stages of the disease patients report the occurrence of fatigue and sleep disorders. Reduced sleep quality and chronic fatigue are common among patients with rheumatoid arthritis. The aim of the research was to evaluate the severity of fatigue and sleep quality assessment among patients hospitalised with rheumatoid arthritis and to determine the relation between the level of symptoms of fatigue and sleep quality and variables such as: age, gender, disease duration, marital status, applied pharmacological treatment, and pain intensity. The study involved 38 patients (12 men and 26 women) hospitalised in the Rheumatologic Ward of the Orthopaedics and Rehabilitation Hospital of the University of Medical Sciences. The average age of the entire group was 56.26 years. Fatigue was evaluated with use of Polish version of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), while in order to evaluate sleep quality within the examined group of patients the Pittsburgh Sleep Quality Index (PSQI) was used. Patients with rheumatoid arthritis in the analysed group have lower sleep quality, and within subjects with such a diagnosis the fatigue is present. The relation was found between fatigue and such variables as: age, illness duration, marital status, applied pharmacological treatment, and severity of pain. Sleep quality within patients with RA is correlated by such variables as: age, gender, applied pharmaceutical treatment, and severity of pain. It was identified that patients with lower sleep quality experience increased levels of fatigue. There is a need to clarify which factors determine the level of fatigue and sleep quality in patients suffering from RA in future population-based research and to indicate to doctors, nurses, psychologists, and physiotherapists the significance and importance of
Arana-Guajardo, Ana; Pérez-Barbosa, Lorena; Vega-Morales, David; Riega-Torres, Janett; Esquivel-Valerio, Jorge; Garza-Elizondo, Mario
Different prediction rules have been applied to patients with undifferentiated arthritis (UA) to identify those that progress to rheumatoid arthritis (RA). The Leiden Prediction Rule (LPR) has proven useful in different UA cohorts. To apply the LPR to a cohort of patients with UA of northeastern Mexico. We included 47 patients with UA, LPR was applied at baseline. They were evaluated and then classified after one year of follow-up into two groups: those who progressed to RA (according to ACR 1987) and those who did not. 43% of the AI patients developed RA. In the RA group, 56% of patients obtained a score ≤ 6 and only 15% ≥ 8. 70% who did not progress to RA had a score between 6 and ≤ 8. There was no difference in median score of LPR between groups, p=0.940. Most patients who progressed to RA scored less than 6 points in the LPR. Unlike what was observed in other cohorts, the model in our population did not allow us to predict the progression of the disease. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.
Viton, J M; Timsit, M; Mesure, S; Massion, J; Franceschi, J P; Delarque, A
To identify how patients with knee arthritis modify their equilibrium and movement control strategies during gait initiation. Observational study. University hospital movement analysis laboratory. Twelve patients with unilateral knee arthritis and 12 healthy control subjects. Durations of the phases of gait initiation (ie, postural, monopodal, and double-support phases), center-of-pressure displacements, ground reaction forces, pelvic velocity, step length, and knee range of motion were measured using a movement analysis system and force plates. Gait initiation was slower in patients than in controls no matter which leg was the supporting one. In patients, the durations of the postural and the monopodal phases were modified in an asymmetrical way according to the leg used as the supporting one. The postural phase was lengthened and the monopodal phase was shortened when the affected leg was the supporting one. Opposite effects were observed when the sound leg was supporting. Step length, knee range of motion, and maximal pelvic velocity were reduced in patients whatever the side of the supporting leg. Gait initiation is an asymmetrical process in unilateral knee arthritis patients, who develop adaptive posturomotor strategies that shorten the monopodal phase on the affected leg.
Pedersen, Elizabeth; Pinsker, Ellie; Younger, Alastair S E; Penner, Murray J; Wing, Kevin J; Dryden, Peter J; Glazebrook, Mark; Daniels, Timothy R
Patients with rheumatoid arthritis often have degeneration of the ankle and ipsilateral hindfoot joints. Patients with rheumatoid arthritis undergoing total ankle arthroplasty have a higher risk of wound breakdown and infection. We compared intermediate-term clinical outcomes after total ankle arthroplasty in patients with rheumatoid arthritis and patients with noninflammatory arthritis. Fifty patients with rheumatoid arthritis were compared with fifty patients with noninflammatory arthritis (the control group), matched for age within ten years, prosthesis type, and follow-up time. All patients underwent total ankle arthroplasty. Revisions and major complications were noted. Outcome scores included the Ankle Osteoarthritis Scale (AOS) and Short Form-36 (SF-36) Health Survey. The groups were similar with respect to body mass index and length of follow-up (mean, 63.8 months for the rheumatoid arthritis group and 65.6 months for noninflammatory arthritis group); the rheumatoid arthritis group was younger (mean, 58.5 years compared with 61.2 years). The mean AOS pain scores were significantly different in the rheumatoid arthritis and noninflammatory arthritis groups preoperatively (p < 0.01), but were similar following total ankle arthroplasty (mean and standard deviation, 18.5 ± 17.8 for the rheumatoid arthritis group and 19.7 ± 16.5 for the noninflammatory arthritis group; p = 0.93). Both groups showed significant improvement (p < 0.05) with regard to the AOS scores for pain and disability and SF-36 physical component summary scores following surgery. Postoperatively, AOS disability and SF-36 physical component summary scores were better for patients with noninflammatory arthritis. There were seven revisions in the rheumatoid arthritis group and five in noninflammatory arthritis group. There was one major wound complication in the rheumatoid arthritis cohort and none in the control cohort. Patients with rheumatoid arthritis benefit from total ankle arthroplasty and
This paper reviews recent approaches to treatment of early rheumatoid arthritis (RA) with disease-modifying antirheumatic drugs (DMARDs). The literature on treatment the early RA published between 1995 and 2007 was accessed through the PubMed database from the National Library of Medicine. Keywords were ‘early rheumatoid arthritis’, ‘disease-modifying antirheumatic drugs’, ‘biologic agents’ and ‘combination therapy’. Only results of trials on human subjects that directly measured the effects of DMARDs or biological agents on clinical, laboratory parameters and radiological progression of early RA were selected. Combination therapy suppresses RA activity and radiological progression more effectively than monotherapy. If better control of RA is evident after 3–6 months of treatment with the combination of DMARDs, one must still decide whether to stop the first DMARD, stop the second, or continue with the combination. Combination therapy biological agents (infliximab, adalimumab) with methotrexate and etanercept therapy alone may induce remission in many patients with early RA. It is a method of choice in patients with an adverse prognosis. The main indications for combination therapy ‘standard’ DMARDs or combination 1 DMARDs with a biological agent are such variables as detection of a shared epitope, increase of concentration of anticyclic citrullinated peptide antibodies, rheumatoid factor, C-reactive protein, 28-joint disease activity score, Sharp score and presence of erosion in joints. The majority of rheumatologists believe that patients with RA should be treated with DMARDs earlier rather than later in the disease process. Further trials should establish the optimal approaches to early RA therapy. PMID:18537958
Chin, Chu Yu; Weng, Meng Yu; Lin, Tzu Chieh; Cheng, Shyr Yuan; Yang, Yea Huei Kao; Tseng, Vincent S.
Rheumatoid arthritis (RA) is a chronic autoimmune rheumatic disease that can cause painful swelling in the joint lining, morning stiffness, and joint deformation/destruction. These symptoms decrease both quality of life and life expectancy. However, if RA can be diagnosed in the early stages, it can be controlled with pharmacotherapy. Although many studies have examined the possibility of early assessment and diagnosis, few have considered the relationship between significant risk factors and the early assessment of RA. In this paper, we present a novel framework for early RA assessment that utilizes data preprocessing, risk pattern mining, validation, and analysis. Under our proposed framework, two risk patterns can be discovered. Type I refers to well-known risk patterns that have been identified by existing studies, whereas Type II denotes unknown relationship risk patterns that have rarely or never been reported in the literature. These Type II patterns are very valuable in supporting novel hypotheses in clinical trials of RA, and constitute the main contribution of this work. To ensure the robustness of our experimental evaluation, we use a nationwide clinical database containing information on 1,314 RA-diagnosed patients over a 12-year follow-up period (1997–2008) and 965,279 non-RA patients. Our proposed framework is employed on this large-scale population-based dataset, and is shown to effectively discover rich RA risk patterns. These patterns may assist physicians in patient assessment, and enhance opportunities for early detection of RA. The proposed framework is broadly applicable to the mining of risk patterns for major disease assessments. This enables the identification of early risk patterns that are significantly associated with a target disease. PMID:25875441
Chin, Chu Yu; Weng, Meng Yu; Lin, Tzu Chieh; Cheng, Shyr Yuan; Yang, Yea Huei Kao; Tseng, Vincent S
Rheumatoid arthritis (RA) is a chronic autoimmune rheumatic disease that can cause painful swelling in the joint lining, morning stiffness, and joint deformation/destruction. These symptoms decrease both quality of life and life expectancy. However, if RA can be diagnosed in the early stages, it can be controlled with pharmacotherapy. Although many studies have examined the possibility of early assessment and diagnosis, few have considered the relationship between significant risk factors and the early assessment of RA. In this paper, we present a novel framework for early RA assessment that utilizes data preprocessing, risk pattern mining, validation, and analysis. Under our proposed framework, two risk patterns can be discovered. Type I refers to well-known risk patterns that have been identified by existing studies, whereas Type II denotes unknown relationship risk patterns that have rarely or never been reported in the literature. These Type II patterns are very valuable in supporting novel hypotheses in clinical trials of RA, and constitute the main contribution of this work. To ensure the robustness of our experimental evaluation, we use a nationwide clinical database containing information on 1,314 RA-diagnosed patients over a 12-year follow-up period (1997-2008) and 965,279 non-RA patients. Our proposed framework is employed on this large-scale population-based dataset, and is shown to effectively discover rich RA risk patterns. These patterns may assist physicians in patient assessment, and enhance opportunities for early detection of RA. The proposed framework is broadly applicable to the mining of risk patterns for major disease assessments. This enables the identification of early risk patterns that are significantly associated with a target disease.
Uno, K.; Matsui, N.; Nohira, K.; Suguro, T.; Kitakata, Y.; Uchiyama, G.; Miyoshi, T.; Uematsu, S.; Inoue, S.; Arimizu, N.
This study evaluates the usefulness of labeled leukocyte imaging in patients with rheumatoid arthritis. In 33 patients, the incidence of pain and swelling in 66 wrist joints and 66 knee joints was compared with the accumulation of (/sup 111/In)leukocytes. No accumulation of (/sup 111/In)leukocytes was seen in any of the patients' wrists (0/12) or knee joints (0/14) when both pain and swelling were absent. In contrast, 93% (25/27) of wrist joints and 80% (24/30) of knee joints with both pain and swelling were positive by (/sup 111/In)leukocyte scintigraphy. There was little correlation between the stage of the disease, as determined by radiography, and (/sup 111/In)leukocyte accumulation. This study suggests that (/sup 111/In)leukocyte imaging may be a reliable procedure for monitoring the activity of rheumatoid arthritis, especially for confirming the lack of an ongoing inflammatory response.
Sandberg, Maria E C; Bengtsson, Camilla; Källberg, Henrik; Wesley, Annmarie; Klareskog, Lars; Alfredsson, Lars; Saevarsdottir, Saedis
To investigate whether overweight/obesity at diagnosis affects the chances of decrease in disease activity and pain in early rheumatoid arthritis (RA). We investigated incident RA cases from the population-based Epidemiological Investigation of risk factors for Rheumatoid Arthritis (EIRA) study (2006-2009, N=495) with clinical follow-up in the Swedish Rheumatology Quality Register. At diagnosis, 93% received disease-modifying antirheumatic drugs (DMARDs) (86% methotrexate). The odds of achieving a good response according to the DAS28-based European League Against Rheumatism (EULAR) criteria, low disease activity (DAS28<3.2), remission (DAS28<2.6) or pain remission (visual analogue scale ≤20 mm) at 3-months and 6-months follow-up, were calculated using logistic regression, adjusting for potential confounders. Significant dose-response relationships were found between Body Mass Index (BMI) and change of disease activity as well as pain at both time points. Patients with BMI ≥25 had 51% lower odds of achieving low disease activity (odds ratio (OR=0.49 (95% CI 0.31 to 0.78)) and 42% lower odds of remission (OR=0.58 (95% CI 0.37 to 0.92)) at the 6-months visit, compared to normal-weight patients. This effect was also present at 3 months, where we also found a 43% decreased odds of pain remission (OR=0.57 (95% CI 0.37 to 0.88)). No effect modification was found for anti-citrullinated protein antibody (CCP)-status, sex, prednisolone treatment or DAS28 at diagnosis. Overweight at diagnosis significantly decreases the chance of achieving good disease control during the early phase of RA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Bello-Gualtero, Juan M; Lafaurie, Gloria I; Hoyos, Lida X; Castillo, Diana M; De-Avila, Juliette; Munevar, Juan C; Unriza, Sonia; Londoño, John; Valle-Oñate, Rafael; Romero-Sánchez, Consuelo
Recent consensus emphasizes the importance of studying individuals at risk for rheumatoid arthritis (pre-RA) and those with early RA (eRA). Periodontal tissues have been recently evaluated, but these studies are limited. To evaluate the periodontal condition, immunoglobulin (Ig)G subclasses against Porphyromonas gingivalis in individuals with pre-RA and eRA were compared with controls to establish an association between periodontal infection markers and rheumatic activity. Rheumatologic and periodontal condition was evaluated in 119 individuals with pre-RA, 48 patients with eRA, and matched controls. P. gingivalis IgG1 and IgG2 were analyzed. C-reactive protein, erythrocyte sedimentation rate (ESR), rheumatoid factor, anticitrullinated protein antibodies (ACPAs), and RA activity were measured. The groups were compared with McNemar test and paired t-test. Conditional logistic regression was performed for pre-RA confounders, and χ(2) test was used to evaluate periodontal variables and RA activity indices. Pre-RA individuals showed significantly higher levels of plaque index (P = 0.01) and bleeding on probing (P = 0.03) and higher severity of periodontal disease (P = 0.02). Periodontitis was associated with pre-RA (odds ratio, 3.39; 95% confidence interval, 1.64 to 7.01) but not with eRA. In pre-RA, P. gingivalis-specific IgG2 was associated with ACPAs (P = 0.049) and disease severity visual analog scale (P = 0.03). In eRA, IgG2 against P. gingivalis was associated with ESR (P = 0.046) and ACPAs (P = 0.04). P. gingivalis was associated with ACPAs (P = 0.04). This study shows that individuals with pre-RA have significant inflammatory periodontal involvement. There was a significant association between IgG against P. gingivalis and ACPAs in pre-RA and markers of RA activity in individuals with eRA.
Ozkan, Yesim; Mete, Guray; Sepici-Dincel, Aylin; Sepici, Vesile; Simsek, Bolkan
Increased kynurenine/tryptophan-reflects trytophan degradation-and neopterin levels have been regarded as a biochemical marker of cell-mediated immune response and inflammation. This study was designed to evaluate the usefulness of tryptophan degradation and neopterin levels in active rheumatoid arthritis patients under therapy. In this case-control study, kynurenine and tryptophan levels were determined by HPLC; neopterin and tumor necrosis factor-α levels were measured with ELISA in 32 active rheumatoid arthritis patients and 20 healthy controls. Although mean values of tryptophan, kynurenine, ratio of kynurenine to tryptophan, neopterin, and tumor necrosis factor-α levels did not show statistically significant differences between patient and control groups, neopterin levels correlated positively with kynurenine (r = 0.582, p < 0.02), kynurenine/tryptophan (r = 0.486, p < 0.05), erythrocyte sedimentation rate (r = 0.472, p < 0.05) and RF (r = 0.478, p < 0.05) in the rheumatoid arthritis group. CRP levels of the patient group correlated with kynurenine levels (r = 0.524, p < 0.03). Determination of tryptophan degradation and neopterin levels in chronic inflammatory disease may provide a better understanding of progression of the disease.
Wang, Xiangcheng; Zhao, Zhenfang; Wang, Tao; Wang, Xuemei; Li, Xiao-Feng
Objectives: To validate 99mTc-labeled arginylglycylaspartic acid (99mTc-3PRGD2) scintigraphy as a means to image synovial neoangiogenesis in joints afflicted by rheumatoid arthritis and to investigate its potential in the early detection and management of rheumatoid arthritis. Methods: Rheumatoid arthritis and osteoarthritis were generated in Sprague Dawley rats by type II collagen immunization and papain injection, respectively. Rats were imaged with 99mTc-3PRGD2 and 99mTc- methyl diphosphonate (99mTc MDP). X-ray images were also obtained and assessed by a radiologist. Immunohistochemistry of αvβ3 and CD31confirmed the onset of synovial neoangiogenesis. The effect of bevacizumab on rheumatoid arthritis was followed with 99mTc-3PRGD2 scintigraphy. A patient with rheumatoid arthritis and a healthy volunteer were scanned with 99mTc-3PRGD2. Results: Two weeks after immunization, a significant increase in 99mTc-3PRGD2 was observed in the joints of the rheumatoid arthritis model though uptake in osteoarthritis model and untreated controls was low. 99mTc-MDP whole body scans failed to distinguish early rheumatoid arthritis joints from healthy controls. The expression of αvβ3 and CD31was significantly higher in the joints of rheumatoid arthritis rats compared to normal controls. In serial 99mTc-3PRGD2 scintigraphy studies, 99mTc-3PRGD2 uptake increased in parallel with disease progression. Bevacizumab anti-angiogenetic therapy both improved the symptoms of the rheumatoid arthritis rats and significantly decreased 99mTc-3PRGD2 uptake. Significantly higher 99mTc-3PRGD2 accumulation was also observed in rheumatoid arthritis joints in the patient. Conclusions: Our findings indicate that 99mTc-3PRGD2 scintigraphy could detect early rheumatoid arthritis by imaging the associated synovial neoangiogenesis, and may be useful in disease management. PMID:27992368
Le Calloch, Ronan; Ianotto, Jean-Christophe; Guillerm, Gaëlle; Tonnelier, Jean Marie
Aplastic anaemia is a rare and serious disease characterised by severe immunosuppression due to prolonged neutropenia and the use of immunosuppressants such as corticosteroids, cyclosporine and antithymocyte globulin. Candida species are pathogens of low virulence colonising the skin and the digestive tract of many healthy individuals. Nonetheless, the incidence of invasive candidal infection is increasing. The widespread use of central intravascular catheters, invasive procedures, broad-spectrum antibiotics and immunosuppresion predisposes patients to these infections. Eye, skin, cardiac, liver, spleen and brain infection are the most common sites of invasive candidiasis. Bone and joint infections are less frequent and Candida hip septic arthritis is extremely rare. We present here a patient treated for aplastic anaemia, who developed fungal arthritis of the hip and systemic candidaemia.
Lee, Jiyeon; Kim, Jung-Hee; Chung, EunJung; Lee, Byoung-Hee
[Purpose] The objective of this study is to provide a direction for efficient management of arthritis through the analysis of multiple factors related to the functional state of patients. [Subjects and Methods] The Visual Analog Scale, Knee Society Knee Score & Function Score, Hospital for Special Surgery, Short Form-36 Health Survey and Western Ontario McMaster Universities Osteoarthritis Index for a total of 135 patients with knee arthritis were determined with a survey. [Results] There is a significant correlation between age, pain, Knee Society Knee Score, Hospital for Special Surgery, Knee Society Function Score, and Western Ontario McMaster Universities Osteoarthritis Index score. [Conclusion] It is necessary to improve the factors that affect knee function and quality of life, and a study on knee joint muscle strength is suggested as a follow-up study. PMID:28265166
Emery, Paul; Solem, Caitlyn; Majer, Istvan; Cappelleri, Joseph C; Tarallo, Miriam
This retrospective medical chart review aimed to provide a current, real-world overview of biologic usage in patients with rheumatoid arthritis (RA) in Germany, Spain, and the UK, and estimate clinical and healthcare utilization outcomes associated with early versus late treatment. Adults (≥18 years) with a confirmed RA diagnosis between January 2008 and December 2010, who received biologic treatment for ≥3 months and had ≥12 months of follow-up were included. Early treatment was receipt of biologic agent ≤1 year after RA diagnosis. Outcomes included 28-joint disease activity score (DAS28) reduction of ≥1.2 from biologic start and remission (DAS28 < 2.6). Time to outcome was evaluated using Kaplan-Meier curves and log-rank tests. Of 328 patients enrolled (Germany [n = 111], Spain [n = 106], UK [n = 111]), 58.2 % received early biologic (Germany: 55.0 %, UK: 55.9 %, Spain: 64.2 %; p = 0.321). First-line biologics were more frequent in Spain (26.4 %) and Germany (19.8 %) versus the UK (7.2 %; p < 0.001). Late-treated patients were hospitalized more often than early-treated patients (10.5 vs 2.9 % [p = 0.006] for 9.0 vs 5.4 mean inpatient days [p = 0.408]). DAS28 was 5.1 at biologic initiation (n = 310); 73.5 % of patients had a DAS28 decrease of ≥1.2 and 44.5 % achieved remission. More patients had DAS28 decrease of ≥1.2 (79.2 vs 65.9 %; p = 0.009) and remission (51.1 vs 35.6 %; p = 0.007) with early versus late treatment, with a significant difference in Kaplan-Meier curves when indexing on time since diagnosis (p < 0.001) and biologic start (p = 0.024). In RA patients receiving biologic therapy, over half received biologic therapy early. Early initiation was associated with improved clinical outcomes and reduced hospitalization rates versus late treatment.
Harigane, Kengo; Mochida, Yuichi; Ishii, Katsushi; Ono, Shigeru; Mitsugi, Naoto; Saito, Tomoyuki
We report a rare case of dystrophic calcinosis in a patient with rheumatoid arthritis in bilateral buttock lesions and the right elbow joint. The calcinosis was surgically removed because it caused severe local pain, possible infection, and difficulty in sitting. Because no recommended standard pharmacotherapy exists for dystrophic calcinosis, surgical treatment should be taken into consideration when calcinosis causes severe local pain or restricts activities of daily life.
Pappy, Reji; Wayangankar, Siddharth; Kalapura, Thomachan; Abu-Fadel, Mazen S.
Coronary artery aneurysm (CAA) formation in the setting of an acute inflammatory state due to connective tissue disease is rare. We report a case of rapid progression from an ectatic to an aneursymatic left circumflex coronary artery leading to an acute coronary event in a patient with rheumatoid arthritis (RA). We report the accelerated growth of the aneurysm as it was temporally related to the lapse in treatment and the management strategies involved with this entity. PMID:21403892
Pappy, Reji; Wayangankar, Siddharth; Kalapura, Thomachan; Abu-Fadel, Mazen S
Coronary artery aneurysm (CAA) formation in the setting of an acute inflammatory state due to connective tissue disease is rare. We report a case of rapid progression from an ectatic to an aneursymatic left circumflex coronary artery leading to an acute coronary event in a patient with rheumatoid arthritis (RA). We report the accelerated growth of the aneurysm as it was temporally related to the lapse in treatment and the management strategies involved with this entity.
Herasymenko, S I; Babko, A M; Poluliakh, M V; Huzhevs'kyĭ, I V; Herasymenko, A S
Brachial joint affection in patients, suffering rheumatoid arthritis, occupies a third place after such of the elbow and the hand. Due to significant reduction of a freedom degree, caused by inflammation, the upper extremity looses function of active instrument for the items transposition. Volume of surgical treatment of such patients depends on stage of the process. On early stages arthroscopic synovectomy of brachial joint is performed and on the late--endoprosthesis. Late results of the treatment are mainly positive. Satisfactory results are based, predominantly, on raising of activity of general rheumatoid inflammation.
Salaffi, Fausto; Carotti, Marina; Ciapetti, Alessandro; Di Carlo, Marco; Gasparini, Stefania; Farah, Sonia; Gutierrez, Marwin
The advent of Internet and World Wide Web has created new perspectives toward interaction between patients and healthcare professionals. Telemonitoring patients with rheumatoid arthritis (RA) is an emerging concept to guide the collaborative management treatment and improve outcomes in patients. The objective of this study was to investigate whether an intensive treatment strategy, according to a telemonitoring protocol, is more effective than conventional management strategy in reaching remission and comprehensive disease control (CDC) after 1 year in early rheumatoid arthritis (ERA) patients. Forty-four ERA patients were randomly allocated into two groups: the telemonitoring intensive strategy (TIS) group (group 1) or the conventional strategy (CS) group (group 2). Three patients refused to participate. In group 1 (n = 21), a remote monitoring system of disease activity, in combination with protocolised treatment adjustments aiming for remission was applied. In group 2 (n = 20), patients were treated according to daily clinical practice, with regular evaluation of disease activity, but without protocolised treatment adjustments. A telemedical care called "REmote TElemonitoring for MAnaging Rheumatologic Condition and HEaltcare programmes" (RETE-MARCHE), was developed to perform the remote monitoring. A higher percentage of patients in the TIS group achieved CDAI remission vs patients in the CS group (38.1 % vs 25 % at year 1, p <0.01). Time to achieve remission was significantly shorter in the group 1 than in the group 2, with a median of 20 weeks vs a median over 36-weeks (p <0.001). Concordantly, the patients in group 1 showed a greater improvement (p <0.001), compared with group 2 in terms of functional impairment (71.4 % vs 35 %) and radiological damage progression (23.8 % vs 10 %), resulting in a greater rate of CDC (19.4 % vs 5 %). According to our results, an intensive treatment strategy by telemonitoring leads to more effective disease
Sanayama, Yoshie; Makita, Sohei; Hosokawa, Junichi; Nakagomi, Daiki; Takabayashi, Katsuhiko
Introduction. This study aimed to investigate the efficacy of abatacept for arthritis in patients with rhupus, an overlap syndrome between rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Methods. Patients who fulfilled both the 2010 ACR/EULAR criteria for RA classification and the 1997 ACR revised criteria for classification of SLE and received abatacept treatment for arthritis were retrospectively studied. Results. Six rhupus patients who fulfilled the inclusion criteria above were identified. All patients had active arthritis despite receiving antirheumatic drugs including methotrexate when abatacept was initiated. Clinical Disease Activity Index (CDAI) significantly decreased between baseline and 12 weeks (P = 0.028) and remained low through 24 weeks. All patients achieved either a good or moderate response according to the EULAR response criteria at 24 weeks. Health Assessment Questionnaire-Disability Index (HAQ-DI) also significantly decreased between baseline and 24 weeks (P = 0.043). In addition, the levels of immunoglobulin G and anti-DNA antibody significantly decreased between baseline and 24 weeks (P = 0.028 and P = 0.043, resp.). Conclusions. Treatment with abatacept is likely to be efficacious in patients with rhupus whose arthritis is refractory to methotrexate. In addition, abatacept may have a moderate effect on abnormal antibody production in rhupus patients. PMID:24324510
Pelaez, Ingris; Infante, Claudia; Quintana, Rosana
Early diagnosis and treatment of rheumatoid arthritis (RA) depends on the degree of fit between the characteristics of the patients and those of the health services. Ensuring timely assessment and treatment is the ideal medical care of RA. The reasons that underlay delays and the help-seeking trajectories are contextually determined. This study aims to identify the empirical evidence related to the help-seeking process and delay in RA in Latin America and to create a comprehensive model integrating the RA medical care processes of help-seeking and delay in a mixed health care system with variable accessibility. Non-systematic literature review of studies with both quantitative and qualitative methodology was conducted. Most of the research about delay and its associated variables have been undertaken in European countries and with White population and cannot be translated to the Latin America context where this research is almost inexistent. These countries have a completely different social context, and for most of the population, the health services are insufficient, inaccessible, fragmented, limited, and inequitable. Our results also show that in RA medical care utilization research, the theories and measurements of the constructs of illness trajectories, help-seeking, and accessibility are not integrated. We offer a conceptual framework that integrates help-seeking trajectories, delay, and accessibility of RA medical health services. If research on RA service utilization is to be undertaken in these countries, there is a need for a comprehensive framework than can enable researchers to integrate and contextualize the study of the problems within broad theoretical and methodological perspectives.
Seoane, Iria V.; Ortiz, Ana M.; Piris, Lorena; Lamana, Amalia; Juarranz, Yasmina; García-Vicuña, Rosario; González-Álvaro, Isidoro; Gomariz, Rosa P.; Martínez, Carmen
Background The vasoactive intestinal peptide (VIP) receptors VPAC1 and VPAC2 mediate anti-inflammatory and immunoregulatory responses in rheumatoid arthritis (RA). Data on the expression of these receptors could complement clinical assessment in the management of RA. Our goal was to investigate the correlation between expression of both receptors and the 28-Joint Disease Activity Score (DAS28) in peripheral blood mononuclear cells (PBMCs) from patients with early arthritis (EA). We also measured expression of IL-6 to evaluate the association between VIP receptors and systemic inflammation. Methods We analyzed 250 blood samples collected at any of the 5 scheduled follow-up visits from 125 patients enrolled in the Princesa Early Arthritis Register Longitudinal study. Samples from 22 healthy donors were also analyzed. Sociodemographic, clinical, and therapeutic data were systematically recorded. mRNA expression levels were determined using real-time PCR. Then, longitudinal multivariate analyses were performed. Results PBMCs from EA patients showed significantly higher expression of VPAC2 receptors at baseline compared to healthy donors (p<0.001). With time, however, VPAC2 expression tended to be significantly lower while VPAC1 receptor expression increased in correlation with a reduction in DAS28 index. Our results reveal that more severe inflammation, based on high levels of IL-6, is associated with lower expression of VPAC1 (p<0.001) and conversely with increased expression of VPAC2 (p<0.001). A major finding of this study is that expression of VPAC1 is lower in patients with increased disease activity (p = 0.001), thus making it possible to differentiate between patients with various degrees of clinical disease activity. Conclusion Patients with more severe inflammation and higher disease activity show lower levels of VPAC1 expression, which is associated with patient-reported impairment. Therefore, VPAC1 is a biological marker in EA. PMID:26881970
Wang, Ming-Yu; Wang, Xian-Bin; Sun, Xue-Hui; Liu, Feng-Li; Huang, Sheng-Chuan
Early diagnosis and management improve the outcome of patients with rheumatoid arthritis (RA). The present study explored the application of high-frequency ultrasound (US) and magnetic resonance imaging (MRI) in the detection of early RA. Thirty-nine patients (20 males and 19 females) diagnosed with early RA were enrolled in the study. A total of 1,248 positions, including 858 hand joints and 390 tendons, were examined by high-frequency US and MRI to evaluate the presence of bone erosion, bone marrow edema (BME), synovial proliferation, joint effusion, tendinitis and tendon sheath edema. The imaging results of the above abnormalities, detected by US, were compared with those identified using MRI. No statistically significant overall changes were observed between high-frequency US and MRI in detecting bone erosion [44 (5.1%) vs. 35 (4.1%), respectively; P>0.05], tendinitis [18 (4.6%) vs. 14 (1.5%), respectively; P>0.05] and tendon sheath edema [37 (9.5%) vs. 30 (7.7%), respectively; P>0.05]. Significant differences were observed between high-frequency US and MRI with regards to the detection of synovial proliferation [132 (15.4%) vs. 66 (7.7%), respectively; P<0.05] and joint effusion [89 (10.4%) vs. 52 (6.1%), respectively; P<0.05]. In addition, significant differences were identified between the detection of BME using MRI compared with high-frequency US (5.5 vs. 0%, respectively; P<0.05). MRI and high-frequency US of the dominant hand and wrist joints were comparably sensitive to bone erosion, tendinitis and tendon sheath edema. However, MRI was more sensitive in detecting bone marrow edema in early RA, while US was more sensitive in the evaluation of joint effusion and synovial proliferation. In conclusion, US and MRI are promising for the detection and diagnosis of inflammatory activity in patients with RA. PMID:27882112
Kratz, Ewa Maria; Borysewicz, Krzysztof; Katnik-Prastowska, Iwona
The expressions of some terminal glycotopes of synovial immunoglobulins G, A, and M were analysed in relation to rheumatoid arthritis (RA) progression defined according to early and advanced radiological changes in patients' hands. The relative amounts of terminal monosaccharides were determined by lectin-immunoblotting of immunoglobulin preparations using appropriate lectins able to recognize alpha2,6-linked (Sambucus nigra agglutinin) and alpha2,3-linked (Maackia amurensis agglutinin) sialic acid, galactose (Ricinus communis agglutinin I), N-acetylglucosamine (Griffonia simplicifolia agglutinin II) as well as alpha1,6-linked (Aleuria aurantia lectin), alpha1,3-linked (Lotus tetragonolobus agglutinin), and alpha1,2-linked (Ulex europaeus agglutinin) fucose. The results indicate differences between early and advanced RA stages in the terminal sugar exposition of synovial IgG and IgA, but not IgM. The galactose-deficient glycotope with exposed N-acetylglucosamine of the synovial 33.1-kDa IgG fragment appeared exclusively in the early stage of RA. In contrast, this glycotope of intact synovial IgG and IgA was present in both groups, although with higher proportions in advanced RA. The proportions of the sialyl and fucosyl determinants of intact synovial A and G immunoglobulins were clearly lower in the early RA group than in the advanced. The analysis of terminal oligosaccharide exposition in IgG, IgG fragments, and IgA present in the synovial fluid of RA patients might be applicable as a stage-specific marker in the diagnosis and therapy of RA patients.
Wang, Ming-Yu; Wang, Xian-Bin; Sun, Xue-Hui; Liu, Feng-Li; Huang, Sheng-Chuan
Early diagnosis and management improve the outcome of patients with rheumatoid arthritis (RA). The present study explored the application of high-frequency ultrasound (US) and magnetic resonance imaging (MRI) in the detection of early RA. Thirty-nine patients (20 males and 19 females) diagnosed with early RA were enrolled in the study. A total of 1,248 positions, including 858 hand joints and 390 tendons, were examined by high-frequency US and MRI to evaluate the presence of bone erosion, bone marrow edema (BME), synovial proliferation, joint effusion, tendinitis and tendon sheath edema. The imaging results of the above abnormalities, detected by US, were compared with those identified using MRI. No statistically significant overall changes were observed between high-frequency US and MRI in detecting bone erosion [44 (5.1%) vs. 35 (4.1%), respectively; P>0.05], tendinitis [18 (4.6%) vs. 14 (1.5%), respectively; P>0.05] and tendon sheath edema [37 (9.5%) vs. 30 (7.7%), respectively; P>0.05]. Significant differences were observed between high-frequency US and MRI with regards to the detection of synovial proliferation [132 (15.4%) vs. 66 (7.7%), respectively; P<0.05] and joint effusion [89 (10.4%) vs. 52 (6.1%), respectively; P<0.05]. In addition, significant differences were identified between the detection of BME using MRI compared with high-frequency US (5.5 vs. 0%, respectively; P<0.05). MRI and high-frequency US of the dominant hand and wrist joints were comparably sensitive to bone erosion, tendinitis and tendon sheath edema. However, MRI was more sensitive in detecting bone marrow edema in early RA, while US was more sensitive in the evaluation of joint effusion and synovial proliferation. In conclusion, US and MRI are promising for the detection and diagnosis of inflammatory activity in patients with RA.
Smolen, Josef S; Aletaha, Daniel; McInnes, Iain B
Rheumatoid arthritis is a chronic inflammatory joint disease, which can cause cartilage and bone damage as well as disability. Early diagnosis is key to optimal therapeutic success, particularly in patients with well-characterised risk factors for poor outcomes such as high disease activity, presence of autoantibodies, and early joint damage. Treatment algorithms involve measuring disease activity with composite indices, applying a treatment-to-target strategy, and use of conventional, biological, and newz non-biological disease-modifying antirheumatic drugs. After the treatment target of stringent remission (or at least low disease activity) is maintained, dose reduction should be attempted. Although the prospects for most patients are now favourable, many still do not respond to current therapies. Accordingly, new therapies are urgently required. In this Seminar, we describe current insights into genetics and aetiology, pathophysiology, epidemiology, assessment, therapeutic agents, and treatment strategies together with unmet needs of patients with rheumatoid arthritis.
Al Maashari, Raghda; Hamodat, Mowafak M
Methotrexate-induced accelerated nodulosis (MIAN) is not an uncommon adverse effect associated with the use of the methotrexate in rheumatoid arthritis. Limited case reports describe panniculitis as a pathological finding in this setting. A 31-year-old female with seropositive rheumatoid arthritis on methotrexate therapy presented with a 2-week history of sudden onset of painful infiltrated subcutaneous nodules on both forearms. Based on clinical and histological findings, a diagnosis of methotrexate-induced panniculitis was made. The majority of MIAN case reports that we reviewed showed characteristic pathological findings of classic rheumatoid nodules; few reported panniculitis as a finding. This case illustrates the importance of recognizing this phenomenon as methotrexate-induced panniculitis should be considered in the differential diagnosis of any patient receiving methotrexate presenting with a recent history of accelerated nodulosis. Discontinuation of methotrexate remains controversial.
A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: the treatment of Early Aggressive Rheumatoid Arthritis Trial.
Moreland, Larry W; O'Dell, James R; Paulus, Harold E; Curtis, Jeffrey R; Bathon, Joan M; St Clair, E William; Bridges, S Louis; Zhang, Jie; McVie, Theresa; Howard, George; van der Heijde, Désirée; Cofield, Stacey S
To assess whether it is better to intensively treat all patients with early rheumatoid arthritis (RA) using combinations of drugs or to reserve this approach for patients who do not have an appropriate response (as determined by a Disease Activity Score in 28 joints using the erythrocyte sedimentation rate [DAS28-ESR] of ≥ 3.2 at week 24) to methotrexate (MTX) monotherapy, and to assess whether combination therapy with MTX plus etanercept is superior to the combination of MTX plus sulfasalazine plus hydroxychloroquine. The Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) study is a 2-year, randomized, double-blind trial. A 2 × 2 factorial design was used to randomly assign subjects to 1 of 4 treatment arms: immediate treatment with MTX plus etanercept, immediate oral triple therapy (MTX plus sulfasalazine plus hydroxychloroquine), or step-up from MTX monotherapy to one of the combination therapies (MTX plus etanercept or MTX plus sulfasalazine plus hydroxychloroquine) at week 24 if the DAS28-ESR was ≥ 3.2. All treatment arms included matching placebos. The primary outcome was an observed-group analysis of DAS28-ESR values from week 48 to week 102. At week 24 (beginning of the step-up period), subjects in the 2 immediate-treatment groups demonstrated a greater reduction in the DAS28-ESR compared with those in the 2 step-up groups (3.6 versus 4.2; P < 0.0001); no differences between the combination-therapy regimens were observed. Between week 48 and week 102, subjects randomized to the step-up arms had a DAS28-ESR clinical response that was not different from that of subjects who initially received combination therapy, regardless of the treatment arm. There was no significant difference in the DAS28-ESR between subjects randomized to oral triple therapy and those randomized to receive MTX plus etanercept. By week 102, there was a statistically significant difference in the change in radiographic measurements from baseline between the group receiving MTX
Ratio of Circulating IFNγ+ “Th17 Cells” in Memory Th Cells Is Inversely Correlated with the Titer of Anti-CCP Antibodies in Early-Onset Rheumatoid Arthritis Patients Based on Flow Cytometry Methods of the Human Immunology Project
Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi
Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic joint inflammation characterized by activated T cells. IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. However, it remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we validated the methods of the Human Immunology Project using only the cell-surface marker through measuring the actual expression of IL-17 and IFNγ. We also evaluated the expression of CD161 in human Th17 cells. We then tried to identify Th17 cells, IL-17+Th17 cells, and IFNγ+Th17 cells in the peripheral blood of early-onset RA patients using the standardized method of the Human Immunology Project. Our findings validated the method and the expression of CD161. The ratio of IFNγ+Th17 cells in memory T cells was inversely correlated to the titers of anti-CCP antibodies in the early-onset RA patients. These findings suggest that Th17 cells play important roles in the early phase of RA and that anti-IL-17 antibodies should be administered to patients with early phase RA, especially those with high titers of CCP antibodies. PMID:27294146
Lambova, Sevdalina Nikolova; Müller-Ladner, Ulf
Background There are limited data about the role of nailfold capillaroscopy in inflammatory arthritis. Objectives To study the role of capillaroscopy in inflammatory arthritis — rheumatoid arthritis (RA), psoriatic arthritis (PsA) and early arthritis. Methods Patients from the following groups were included in the study: 62 patients with RA; 34 patients with PsA with involvement of the joints of the hands; 9 women with early arthritis. Nailfold capillaroscopy was performed with videocapillaroscope. Results Raynaud's phenomenon (RP) was found in 30.6% (19/62) of RA patients, in 32.4% (11/34) of PsA patients and 44.4%, (4/9) of cases with early arthritis. The most frequent found capillaroscopic changes in RA patients were presence of elongated capillaries in 58% of cases (36/62) and prominent subpapillary plexus in 69% (43/62). Dilated capillaries were found in 78.9% (15/19) of patients with secondary RP and in 62.8% (27/43) of those without RP. “Scleroderma-like” capillaroscopic pattern was observed with low frequency in RA patients (14.5%/9/62). “Scleroderma-like” capillaroscopic pattern was also found in 11.1% (1/9) in the group of patients with early arthritis. The low frequency of the last type of capillaroscopic pattern in RA requires patients with such changes to be observed during regular follow-up for the development of systemic rheumatic disease different from inflammatory arthritis. In patients with PsA capillaries with specific morphology (tight terminal convolutions) were found in 58.8% (20/34) of cases. Conclusions Results from the present study confirm the necessity for inclusion of the nailfold capillaroscopy in the diagnostic algorithm in patients with inflammatory arthritis. PMID:22426123
Sheehy, C; Gaffney, K; Mukhtyar, C
Patients with rheumatoid arthritis (RA) suffer progressive loss of hand function and have weaker hand grip than the healthy population. In this study we aimed to validate hand grip strength standardized by age and gender (z score) against currently accepted clinical measures of disease activity. Electronic records of patients with a diagnosis of RA seen between April 2007 and December 2011 were screened for the documentation of tender and swollen joint counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), along with patient global activity score and grip strength. Bilateral grip strengths were converted to z scores on the basis of previously published age- and gender-corrected normative data for grip strength. The z scores were then correlated against components of disease activity scores. Ninety patients diagnosed with RA had been seen 602 times within 2 years of diagnosis. Hand grip data were available for 204 visits. There was a statistically significant inverse correlation between grip strength z scores and the tested variables. The sensitivity and specificity of a hand grip z score of -1.5 for predicting remission were, respectively, 70% and 76% for the right hand and 82% and 69% for the left hand. Hand grip testing and subsequent conversion to z scores corrected for age and gender correlate with disease activity in early RA. We have shown that the grip strength z scores can discriminate between various disease states, and the strength seems to return to near normative data when the disease is in remission.
Sag, Sinem; Sag, Mustafa Serdar; Tekeoglu, Ibrahim; Kamanli, Ayhan; Nas, Kemal; Aydın, Yıldıray
We aimed to analyse the nailfold capillaryscopy findings morphologically and examine their relationship with disease activity and demographic characteristics in patients with rheumatoid arthritis. In accordance with the 2010 ACR/EULAR classification criteria, 201 patients diagnosed with Romatoiad artrit (RA) and 50 healthy controls were included. We analysed capillaroscopic abnormalities such asmegacapillaries, haemorrhages, ramifications and avascular areas in patients affected with rheumatoid arthritis. The findings in our study are as follows: in 45.77% of the RA patients, there were nonspecific capillaryscopy findings. When compared to control group, the incidence of tortuosity, dilated capillary and bushy capillary was higher in RA patients (p values, respectively, 0.110, 0.330, 0.440 and 0.516). In RA patients with Raynaud's phenomenon, the incidence of nonspecific capillaryscopy findings was higher. While there is a weak relationship between tortuosity and the duration of disease, no significant relation was detected between capillaryscopy findings and parameters such as RF, anti-CCP positivity and disease activity score (DAS28). When compared to controls, we have detected that RA patients have more nonspecific capillaryscopic findings. We could not find a relationship between nonspecific capillaryscopic findings and RA'a clinical findings and laboratory parameters. There is a need for a long-term wider-scale follow-up study to investigate whether there is a capillaryscopic pattern that can be correlated with RA's clinical findings.
Jatuworapruk, Kanon; Lhakum, Panomkorn; Pattamapaspong, Nuttaya; Kasitanon, Nuntana; Wangkaew, Suparaporn; Louthrenoo, Worawit
Abstract Currently, there are 5 existing classification criteria for gout: the Rome, New York, American Rheumatism Association (ARA), Mexico, and Netherlands criteria. This study was carried out to determine the performance of these classification criteria in Thai patients presenting with acute arthritis. All consecutive patients presenting with acute arthritis and being consulted at the Rheumatology Unit, Chiang Mai University Hospital from January 2013 to May 2015 were invited to join the study. Gout was defined by the presence of monosodium urate crystals in the synovial fluid or tissue examined by experienced rheumatologists. The 5 existing gout classification criteria were performed and evaluated in all of the patients, who were divided in subgroups of early disease (≤2 years), established disease (>2 years), and those without tophus. There were 136 gout and 97 nongout patients. Sensitivity and specificity across all criteria ranged from 75.7% to 97.1% and 68.0% to 84.5%, respectively. Overall, the Mexico criteria had the highest sensitivity (97.1%), and the ARA survey criteria the highest specificity (84.5%), whereas the Mexico criteria performed well in early disease with sensitivity and specificity of 97.1% and 81.7%, respectively. All 5 criteria showed high sensitivity (from 76.4% to 99.1%) but low specificity (from 30.8% to 65.4%) in established disease. In patients without tophus, the sensitivity and specificity ranged from 64.1% to 95.7% and 68.8% to 85.4%, respectively. The ARA survey criteria across all groups showed consistently high specificity for gout. The 5 existing classification criteria for gout had limited sensitivity and specificity in Thai patients presenting with acute arthritis. The ARA survey criteria are the most suitable for diagnosing gout in Thai people when crystal identification is not available. PMID:26844519
Jatuworapruk, Kanon; Lhakum, Panomkorn; Pattamapaspong, Nuttaya; Kasitanon, Nuntana; Wangkaew, Suparaporn; Louthrenoo, Worawit
Currently, there are 5 existing classification criteria for gout: the Rome, New York, American Rheumatism Association (ARA), Mexico, and Netherlands criteria. This study was carried out to determine the performance of these classification criteria in Thai patients presenting with acute arthritis.All consecutive patients presenting with acute arthritis and being consulted at the Rheumatology Unit, Chiang Mai University Hospital from January 2013 to May 2015 were invited to join the study. Gout was defined by the presence of monosodium urate crystals in the synovial fluid or tissue examined by experienced rheumatologists. The 5 existing gout classification criteria were performed and evaluated in all of the patients, who were divided in subgroups of early disease (≤2 years), established disease (>2 years), and those without tophus.There were 136 gout and 97 nongout patients. Sensitivity and specificity across all criteria ranged from 75.7% to 97.1% and 68.0% to 84.5%, respectively. Overall, the Mexico criteria had the highest sensitivity (97.1%), and the ARA survey criteria the highest specificity (84.5%), whereas the Mexico criteria performed well in early disease with sensitivity and specificity of 97.1% and 81.7%, respectively. All 5 criteria showed high sensitivity (from 76.4% to 99.1%) but low specificity (from 30.8% to 65.4%) in established disease. In patients without tophus, the sensitivity and specificity ranged from 64.1% to 95.7% and 68.8% to 85.4%, respectively. The ARA survey criteria across all groups showed consistently high specificity for gout.The 5 existing classification criteria for gout had limited sensitivity and specificity in Thai patients presenting with acute arthritis. The ARA survey criteria are the most suitable for diagnosing gout in Thai people when crystal identification is not available.
Bari, M A; Sutradhar, S R; Sarker, C N; Ahmed, S; Miah, A H; Alam, M K; Hasan, M J; Tariquzzaman, M; Shamsi, S
The present cross-sectional study was conducted in the Department of Medicine, Mymensingh Medical College Hospital, Mymensingh from December 2009 to November 2010 to find out the association of iron deficiency, in anaemia with rheumatoid arthritis and to find a sensitive and less invasive marker to differentiate iron deficiency anaemia from the anaemia of chronic disease. A total of 45 patients of rheumatoid arthritis were provisionally included in the study. Of them, 12 patients were excluded as they did not allow for aspirating the bone marrow, leaving 33 patients to complete the study. The mean age of the patients was 42.6 years (22-66 years) with female to male ratio being roughly 3:1. Majority (97%) of the patients presented weakness followed by 78.8% dizziness, 54.5% palpitation, 24.2% pallor, 12.1% breathlessness, another 12.1% smooth tongue and 6.1% nail change. About 79% of the patients were positive for RA test and nearly 70% of patient had moderate anaemia. The mean serum ferritin was significantly reduced in patients with hypochromic with or without microcytic anaemia than that with normocytic normochromic anaemia (p<0.001). While total iron binding capacity was found to be significantly increased in patients with iron deficiency anaemia than that in patients with anaemia of chronic disease (p<0.021). The serum iron level was considerably reduced in the former group than that in the later group (p<0.066). Bone marrow iron grading revealed 48.5% of the patients with iron depleted and 51.5% with iron repleted. Serum ferritin level of patients with iron depleted bone marrow was significantly decreased than that in patients with iron repleted bone marrow (p<0.001). Serum iron level of the former group was also reduced than that of the later group (p<0.133). Total iron binding capacity was significantly raised in patients with iron depleted group than that in patients with iron repleted group (p<0.001). The study finds that anaemia of chronic disease and
Wabe, Nasir; Sorich, Michael J; Wechalekar, Mihir D; Cleland, Leslie G; McWilliams, Leah; Lee, Anita; Spargo, Llewellyn; Metcalf, Robert G; Hall, Cindy; Proudman, Susanna M; Wiese, Michael D
Treat-to-target (T2T) strategies using a protocol of pre-defined adjustments of disease-modifying anti-rheumatic drugs (DMARDs) according to disease activity improve outcomes for patients with rheumatoid arthritis (RA). However, successful implementation may be limited by deviations from the protocol. The aim of this study was to determine the prevalence of protocol deviation, explore the reasons and identify subsets of patients in whom treatment protocols are more difficult to follow. In this retrospective cohort study, treatment-naïve patients with RA of less than one year's duration, attending a dedicated early arthritis clinic between 2001 and 2013, were followed for three years from initiation of combination therapy with conventional DMARDs which was subsequently modified according to a T2T protocol. At each clinic visit, whether deviation from the protocol occurred, the type of deviation and the reasons for deviation were assessed. The relationship between protocol deviations and baseline variables was determined using linear regression analysis. In total, 198 patients contributed 3,654 clinic visits. The prevalence of protocol deviations was 24.5% and deviation in at least at one clinic visit was experienced by 90.4% of patients. The median time to first deviation was 30 weeks. Continuing existing treatment rather than intensifying therapy was the most common type of deviation (59.9%). Patient and physician related factors were the most common reasons for deviation, each accounting for 24.7% of deviations, followed by toxicities (23.3%) and comorbidities (20.0%). The prevalence of protocol deviations was lower among patients who achieved remission after three years (13.1%; 162 deviations out of 1,228 visits) compared with those who were not in remission (30.9%; 523/1692) (P<0.0001). On multivariate analysis, only body mass index (P=0.003) and helplessness score (P=0.04) were independent predictors of protocol deviations although the predictive power of the
Thomsen, Tanja; Beyer, Nina; Aadahl, Mette; Hetland, Merete L.; Løppenthin, Katrine; Midtgaard, Julie; Esbensen, Bente A.
Background Despite increasing interest in investigating sedentary behaviour (SB) in the general population and in patients with rheumatoid arthritis (RA), there is little documentation of the subjective experiences of SB in patients with RA. This study aimed to examine how patients with RA describe their daily SB. Methods Fifteen patients with RA (10 women and 5 men) from 23 to 73 years of age and with a disease duration ranging from 4 to 27 years were interviewed following a semi-structured interview guide. Data were analysed using the content analysis method described by Graneheim. Results SB appeared in three categories covering: 1) A constant battle between good and bad days; SB could be a consequence of RA in terms of days with pronounced pain and fatigue resulting in many hours of SB. 2) Adaptation to everyday life; living with the unpredictability of RA included constant modification of physical activity level causing increase in SB, especially during periods of disease flare. Prioritizing and planning of SB also functioned as part of self-management strategies. 3) It has nothing to do with my arthritis; for some patients, SB was not related to RA, but simply reflected a way of living independent of the disease. Conclusions SB is perceived, motivated, and performed differently in patients with RA. An individually tailored approach may be essential in understanding and encouraging patients’ motivation towards sustainable change in SB and activity patterns. PMID:26462971
Ikeuchi, Hidekazu; Umemoto, Azusa; Tsukida, Mayuko; Sakurai, Noriyuki; Maeshima, Akito; Kuroiwa, Takashi; Hiromura, Keiju; Nojima, Yoshihisa
While tumor necrosis factor (TNF) inhibitors have dramatically improved the clinical outcomes of rheumatoid arthritis (RA) in recent years, infectious complications are a serious concern. Adalimumab (ADA) is a newly-developed human monoclonal antibody against TNF-alpha. Here we report 2 cases of pneumocystis pneumonia (PCP) which developed in RA patients during ADA therapy. One patient is a 66-year-old woman who had a history of RA for 6 months. The patient was given ADA at 40 mg biweekly for her active arthritis which had been refractory to 6 mg/week of methotrexate (MTX), and 5 mg/day of prednisolone (PSL). One hundred and six days later, she was admitted to our hospital because of fever, cough, and dyspnea. Another patient is a 62-year-old man who had a history of RA for 3 years. Since his arthritis was so active even under the treatment with MTX (8 mg/week) and PSL (15 mg/day), the patient started to be given ADA at 40 mg biweekly. After 28 days, the patient was admitted to the hospital because of dyspnea. Chest roentgenogram and computed tomography revealed interstitial pneumonia in both patients. Beta-D-glucan levels were so high in their serum suggesting the diagnosis of PCP, which was confirmed by the detection of Pneumocystis jirovecii DNA in the sputa by polymerase chain reaction. The patients were immediately treated with sulfamethoxazole/trimethoprim and high-dose prednisolone, which successfully improved pneumonia, and they were discharged from the hospital on the 8(th) and 16(th) day, respectively. PCR and β-D-glucan were useful for the early diagnosis of PCP and lead to the timely induction of adequate treatment and the rescue of these patients.
Choy, E H S; Smith, C M; Farewell, V; Walker, D; Hassell, A; Chau, L; Scott, D L
Treating early active rheumatoid arthritis (RA) with disease modifying antirheumatic drug (DMARD) monotherapy achieves incomplete outcomes and intensive treatment seems preferable. As the relative benefits of combining two DMARDs, one DMARD with glucocorticoids and two DMARDs with glucocorticoids are uncertain we defined them in a factorial trial. A 2-year randomised double-blind factorial trial in patients with RA within 2 years of diagnosis treated with methotrexate studied the benefits of added ciclosporin, 9 months intensive prednisolone or both (triple therapy). The primary outcome was the number of patients with new erosions. Secondary outcomes included Larsen's x-ray scores, disability, quality of life and adverse events. 1391 patients were screened and 467 randomised. Over 2 years 132 (28%) changed therapy and 88 (19%) were lost to follow-up. The number of patients with new erosions was reduced by nearly half by adding ciclosporin or prednisolone (p = 0.01 and 0.03); both treatments reduced increases in Larsen's x-ray scores by over 2 units (p = 0.008 and 0.003). A further reduction in erosive damage was seen with combined use of both treatments. Their effects on erosive damage appeared independent. Triple therapy reduced disability and improved quality of life compared with methotrexate; ciclosporin and prednisolone acted synergistically. More patients withdrew because of adverse events with triple therapy, without an increase in serious adverse effects. This study confirms the existence of a "window of opportunity" in early RA, when intensive combination therapy produces sustained benefits on damage and disability. Although methotrexate-prednisolone combinations reduce erosive damage, the synergistic effect of two DMARDs is needed to improve quality of life.
Lahesmaa-Rantala, R; Magnusson, K E; Granfors, K; Leino, R; Sundqvist, T; Toivanen, A
The passive intestinal permeability of patients with yersinia triggered reactive arthritis was studied using different sized polyethylene glycols (PEGs) contained in a mixture of PEG 400 and PEG 1000. The investigation was carried out at least one year after the onset of yersinia infection, and patients had neither acute gastrointestinal nor joint symptoms. The control groups included patients with uncomplicated yersiniosis as well as healthy subjects who were either HLA-B27 positive or negative. An altered intestinal barrier function to PEG molecules was detected in patients with a history of yersinia infection compared with healthy controls. No significant differences in the permeability were found between patients with or without reactive arthritis, nor was there any association of increased permeability with HLA-B27. The passive permeability of the intestinal mucosa to the larger molecules was increased for an unexpectedly long time after the acute yersinia infection, probably contributing to the perpetuation of joint symptoms in subjects susceptible to a chronic joint disease. PMID:1998397
Äyräväinen, Leena; Leirisalo-Repo, Marjatta; Kuuliala, Antti; Ahola, Kirsi; Koivuniemi, Riitta; Meurman, Jukka H; Heikkinen, Anna Maria
To investigate the association between rheumatoid arthritis (RA) and periodontitis with special emphasis on the role of antirheumatic drugs in periodontal health. Prospective follow-up study. Patients with early untreated RA and chronic active RA were examined at baseline and 16 months later. Controls were examined once. The study was conducted in Finland from September 2005 to May 2014 at the Helsinki University Hospital. Overall, 124 participants were recruited for dental and medical examinations: 53 were patients with early disease-modifying antirheumatic drug (DMARD) naїve RA (ERA), 28 were patients with chronic RA (CRA) with insufficient response to conventional DMARDs. After baseline examination, patients with ERA started treatment with synthetic DMARDs and patients with CRA with biological DMARDs. Controls were 43 age-matched, gender-matched and community-matched participants. Degree of periodontitis (defined according to the Center for Disease Control and Prevention and the American Academy of Periodontology). Prevalence of periodontal bacteria (analysed from plaque samples), clinical rheumatological status by Disease Activity Score, 28-joint count (DAS28), function by Health Assessment Questionnaire (HAQ) and treatment response by European League Against Rheumatism (EULAR) criteria. Moderate periodontitis was present in 67.3% of patients with ERA, 64.3% of patients with CRA and 39.5% of control participants (p=0.001). Further, patients with RA had significantly more periodontal findings compared with controls, recorded with common periodontal indexes. In the re-examination, patients with RA still showed poor periodontal health in spite of treatment with DMARDs after baseline examination. The prevalence of Porphyromonas gingivalis was higher in patients with ERA with periodontal probing depth ≥4 mm compared with patients with CRA and controls. Antirheumatic medication did not seem to affect the results. Moderate periodontitis was more frequent in
Äyräväinen, Leena; Leirisalo-Repo, Marjatta; Kuuliala, Antti; Ahola, Kirsi; Koivuniemi, Riitta; Meurman, Jukka H; Heikkinen, Anna Maria
Objectives To investigate the association between rheumatoid arthritis (RA) and periodontitis with special emphasis on the role of antirheumatic drugs in periodontal health. Design Prospective follow-up study. Patients with early untreated RA and chronic active RA were examined at baseline and 16 months later. Controls were examined once. Settings and participants The study was conducted in Finland from September 2005 to May 2014 at the Helsinki University Hospital. Overall, 124 participants were recruited for dental and medical examinations: 53 were patients with early disease-modifying antirheumatic drug (DMARD) naїve RA (ERA), 28 were patients with chronic RA (CRA) with insufficient response to conventional DMARDs. After baseline examination, patients with ERA started treatment with synthetic DMARDs and patients with CRA with biological DMARDs. Controls were 43 age-matched, gender-matched and community-matched participants. Outcome measures Degree of periodontitis (defined according to the Center for Disease Control and Prevention and the American Academy of Periodontology). Prevalence of periodontal bacteria (analysed from plaque samples), clinical rheumatological status by Disease Activity Score, 28-joint count (DAS28), function by Health Assessment Questionnaire (HAQ) and treatment response by European League Against Rheumatism (EULAR) criteria. Results Moderate periodontitis was present in 67.3% of patients with ERA, 64.3% of patients with CRA and 39.5% of control participants (p=0.001). Further, patients with RA had significantly more periodontal findings compared with controls, recorded with common periodontal indexes. In the re-examination, patients with RA still showed poor periodontal health in spite of treatment with DMARDs after baseline examination. The prevalence of Porphyromonas gingivalis was higher in patients with ERA with periodontal probing depth ≥4 mm compared with patients with CRA and controls. Antirheumatic medication did not seem
Mrabet, Dalila; Laadhar, Lilia; Haouet, Slim; Sahli, Héla; Zouari, Béchir; Makni, Sondès; Sellami, Slaheddine
Autoantibodies to citrullinated proteins (ACPA) are specifically associated with rheumatoid arthritis (RA) and seem to play an important role in its pathogenesis. The specific immunological conflict between ACPA and citrullinated fibrin plays a major role in the self-maintenance of synovial inflammation by forming fibrin deposits in the synovial tissue. These deposits, secondarily citrullinated by a local peptidylarginine deiminase (PADI) enzyme activity, seem to maintain the immunological conflict and the inflammation. Our objective in this work is to study the anomalies of citrullination in a group of patients with early RA, in comparison with a control group of patients suffering from undetermined inflammatory arthritis, osteoarthritis and spondyloarthropathy. For this purpose, we used an enzyme-linked immunosorbent assay (ELISA) to determine the levels of ACPA in serum and synovial fluid. By immunohistochemistry, subtype 4 of PADI was also sought in the synovial biopsies taken from all our patients. We found that the ACPA levels in serum and synovial fluid were significantly higher in patients with RA. The enzyme PADI4 was found only in the group with RA and was statistically correlated with ACPA mean levels in sera and synovial fluid. The expression of PADI4 seems to correlate with intra-synovial deposits of fibrin in RA. However, determination of synovial ACPA levels and detection of intra-synovial PADI4 deposits are of no additional benefit compared with assessment of ACPA levels in serum for the diagnosis of early RA.
Llamas-Covarrubias, MA; Valle, Y; Bucala, R; Navarro-Hernández, RE; Palafox-Sánchez, CA; Padilla-Gutiérrez, JR; Parra-Rojas, I; Bernard-Medina, AG; Reyes-Castillo, Z; Muñoz-Valle, JF
Macrophage migration inhibitory factor (MIF) is an upstream pro-inflammatory cytokine that is associated with the pathogenesis of autoimmune inflammatory diseases including rheumatoid arthritis (RA).Two polymorphisms in the upstream region exist in the MIF gene and are associated with RA susceptibility or severity in different populations. In this case-control study, we investigated whether MIF polymorphisms are associated with RA susceptibility or activity in a western Mexican population .The relationship of MIF levels with clinical features of disease also was assessed. Genotyping of the -794 CATT5-8(rs5844572) and the -173 G>C (s755622) polymorphisms was performed by PCR and PCR-RFLP respectively on 226 RA patients and 210 healthy subjects. Serum MIF levels were determined by ELISA. We found a significant association between the -794 CATT5-8 6,7 MIF genotype with RA. Moreover, we detected an association between the -794 CATT7 allele with early onset RA. The -794 CATT7 and -173*C alleles, which are in linkage disequilibrium, were associated with high disease activityon RA patients. A positive correlation between circulating MIF levels and C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, anti-citrullinated protein/peptides antibodies and TNFα was detected. MIF levels appear to be associated with disease progression rather than disease activity, which is distinct from the established relationship between disease activity and TNFα levels. In conclusion, the MIF gene and protein are associated with RA in a western Mexican population, with a main contribution onto early onset and early stages of disease. PMID:23402792
Collaud Basset, Sabine; Boers, Maarten; Breedveld, Ferdinand; Edwards, Christopher J; Kvien, Tore K; Miossec, Pierre; Sokka-Isler, Tuulikki; van Vollenhoven, Ronald F; Abadie, Eric C; Bruyère, Olivier; Cooper, Cyrus; Mäkinen, Heidi; Thomas, Thierry; Tugwell, Peter; Reginster, Jean-Yves
The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases convened a task force of experts in rheumatoid arthritis (RA) and clinical trial methodology to comment on the new draft ‘Guideline on clinical investigation of medicinal products for the treatment of RA’ released by the European Medicines Agency (EMA). Special emphasis was placed by the group on the development of new drugs for the treatment of early RA. In the absence of a clear definition of early RA, it was suggested that clinical investigations in this condition were conducted in disease-modifying antirheumatic drugs naïve patients with no more than 1 year disease duration. The expert group recommended using an appropriate improvement in disease activity (American College of Rheumatology (ACR) or Simplified/Clinical Disease Activity Index (SDAI/CDAI) response criteria) or low disease activity (by any score) as primary endpoints, with ACR/European League Against Rheumatism remission as a secondary endpoint. Finally, as compelling evidence showed that the Disease Acrivity Score using 28-joint counts (DAS28) might not provide a reliable definition of remission, or sometimes even low disease activity, the group suggested replacing DAS28 as a measurement instrument to evaluate disease activity in RA clinical trials. Proposed alternatives included SDAI, CDAI and Boolean criteria. PMID:27037326
Smolen, Josef S; Collaud Basset, Sabine; Boers, Maarten; Breedveld, Ferdinand; Edwards, Christopher J; Kvien, Tore K; Miossec, Pierre; Sokka-Isler, Tuulikki; van Vollenhoven, Ronald F; Abadie, Eric C; Bruyère, Olivier; Cooper, Cyrus; Mäkinen, Heidi; Thomas, Thierry; Tugwell, Peter; Reginster, Jean-Yves
The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases convened a task force of experts in rheumatoid arthritis (RA) and clinical trial methodology to comment on the new draft 'Guideline on clinical investigation of medicinal products for the treatment of RA' released by the European Medicines Agency (EMA). Special emphasis was placed by the group on the development of new drugs for the treatment of early RA. In the absence of a clear definition of early RA, it was suggested that clinical investigations in this condition were conducted in disease-modifying antirheumatic drugs naïve patients with no more than 1 year disease duration. The expert group recommended using an appropriate improvement in disease activity (American College of Rheumatology (ACR) or Simplified/Clinical Disease Activity Index (SDAI/CDAI) response criteria) or low disease activity (by any score) as primary endpoints, with ACR/European League Against Rheumatism remission as a secondary endpoint. Finally, as compelling evidence showed that the Disease Acrivity Score using 28-joint counts (DAS28) might not provide a reliable definition of remission, or sometimes even low disease activity, the group suggested replacing DAS28 as a measurement instrument to evaluate disease activity in RA clinical trials. Proposed alternatives included SDAI, CDAI and Boolean criteria.
Willard, K.E.; Thorsrud, A.K.; Munthe, E.; Jellum, E.
Human leukocyte proteins from more than 150 patients with rheumatoid arthritis, together with age- and sex-matched controls, were analyzed by use of the ISO-DALT technique of two-dimensional polyacrylamide gel electrophoresis. Patients with ankylosing spondylitis, polymyalgia rheumatica, psoriatic arthritis, calcium tendinitis, post-infectious arthritis, and asymmetrical seronegative arthritis were also included as positive controls. Synthesis of several proteins, referred to by number as members of the Rheuma set, is shown to increase in the leukocyte preparations from patients with classical rheumatoid arthritis. Several of these proteins are specific to monocytes or granulocytes; others are of unknown cellular origin, but appear to be unique to rheumatoid arthritis. The Rheuma proteins appear to be indicators of disease activity, because their increased synthesis can be correlated with sedimentation rate and other clinical indices of rheumatoid disease activity.
Meyer, O; Labarre, C; Dougados, M; Goupille, P.; Cantagrel, A; Dubois, A; Nicaise-Roland, P; Sibilia, J; Combe, B
Objective: To study the value of antibodies to citrullinated proteins/peptides for predicting joint outcomes in patients with recent onset rheumatoid arthritis (RA). Methods: 191 patients with RA onset within the past year were followed up prospectively for five years. Serum samples obtained from 145 patients at baseline before disease modifying antirheumatic drug treatment were examined using three anticitrullinated protein/peptide antibody assays: antiperinuclear factor (APF) by indirect immunofluorescence (IIF), antikeratin antibodies (AKA) by IIF, and anti-cyclic citrullinated peptide (CCP) antibodies by enzyme linked immunosorbent assay (ELISA). Radiographs of the hands and feet taken at baseline and after three and five years were evaluated using Sharp scores modified by van der Heijde. Results:Anti-CCP ELISA was positive in 58.9% of patients. APF/anti-CCP agreement was 77%. The likelihood of a total Sharp score increase after five years was significantly greater among patients with anti-CCP antibodies (67%; odds ratio (OR) 2.5; 95% confidence interval (95% CI) 1.2 to 5.0) or APF (57%; OR 2.4; 95% CI 1.2 to 4.9) but not rheumatoid factor (RF; OR 0.7; 95% CI 0.3 to 1.5). Mean values for radiographic damage, erosion, and joint narrowing scores at the three times were significantly higher in patients with anti-CCP or APF than in those without. AKA did not significantly predict radiographic damage. In separate analyses of patients with and without RF, anti-CCP or APF was better than RF for predicting total joint damage and joint damage progression after five years. Conclusion: Antibodies to citrullinated proteins/peptides determined early in the course of RA by APF IIF or anti-CCP ELISA are good predictors of radiographic joint damage. Further studies of clinical, laboratory, and genetic parameters are needed to improve RA outcome prediction in clinical practice. PMID:12525380
Chen, Jiaxi; Jun, Li; Shiyong, Chen; Li, Hou; Zhu, Ming; Shen, Bo
Immune system activation is known to be involved in the progression of rheumatoid arthritis (RA). The aim of this work was to study the imbalance expressions of indoleamine 2,3-dioxygenase (IDO) and tryptophanyl-tRNA synthetase (TTS) with RA patients. Forty-nine RA patients and 49 healthy controls were studied. The expressions of IDO and TTS were analyzed by real-time quantitative polymerase chain reaction and flow cytometry in peripheral blood mononuclear cells. The expression of TTS mRNA increased significantly in RA patients when compared with healthy controls and correlated with erythrocyte sedimentation rate (r = 0.424, P < 0.01). In addition, we found TTS increased significantly mainly in CD3(+) T cells in rheumatoid arthritis group. Increased TTS expressions from CD3(+) T cells might link to a pathogenic mechanism involved in increasing survival of autoreactive T cells in RA patients. Determination of expressions of TTS may provide a better understanding of progression of the disease.
Alomari, Mahmoud A; Keewan, Esraa F; Shammaa, Rania A; Alawneh, Khaldoon; Khatib, Said Y; Welsch, Michael A
To examine the relationship of handgrip strength with forearm blood flow (BF) and vascular resistance (VR) in rheumatoid arthritis (RA) patients. Forearm BF at rest (RBF) and after upper arm occlusion (RHBF), and handgrip strength were examined in 78 individuals (RA = 42 and controls (CT) = 36). Subsequently, VR at rest (RVR) and after occlusion (RHVR) were calculated. The patients' RBF (P = 0.02) and RHBF (P = 0.0001) were less, whereas RVR (P = 0.002) and RHVR (P = 0.0001) were greater as compared to the CTs. Similarly, handgrip strength was lower in the RAs (P = 0.0001). Finally, handgrip strength was directly associated with RBF (r = 0.43; P = 0.0001), and RHBF (r = 0.5; P = 0.0001), and inversely related to RVR (r = -0.3; P = 0.009) and RHVR (r = -0.3; P = 0.007). The present study uniquely identifies an association between regional measures of forearm blood flow and handgrip strength in patients and healthy control. In addition, this study confirms the presence of vascular and muscle dysfunction in patients with rheumatoid arthritis, as evidenced by lower forearm blood flow indices, at rest and following occlusion, and lower handgrip strength as compared to healthy individuals.
Alomari, Mahmoud A.; Keewan, Esraa F.; Shammaa, Rania A.; Alawneh, Khaldoon; Khatib, Said Y.; Welsch, Michael A.
Objective. To examine the relationship of handgrip strength with forearm blood flow (BF) and vascular resistance (VR) in rheumatoid arthritis (RA) patients. Methods. Forearm BF at rest (RBF) and after upper arm occlusion (RHBF), and handgrip strength were examined in 78 individuals (RA = 42 and controls (CT) = 36). Subsequently, VR at rest (RVR) and after occlusion (RHVR) were calculated. Results. The patients' RBF (P = 0.02) and RHBF (P = 0.0001) were less, whereas RVR (P = 0.002) and RHVR (P = 0.0001) were greater as compared to the CTs. Similarly, handgrip strength was lower in the RAs (P = 0.0001). Finally, handgrip strength was directly associated with RBF (r = 0.43; P = 0.0001), and RHBF (r = 0.5; P = 0.0001), and inversely related to RVR (r = −0.3; P = 0.009) and RHVR (r = −0.3; P = 0.007). Conclusion. The present study uniquely identifies an association between regional measures of forearm blood flow and handgrip strength in patients and healthy control. In addition, this study confirms the presence of vascular and muscle dysfunction in patients with rheumatoid arthritis, as evidenced by lower forearm blood flow indices, at rest and following occlusion, and lower handgrip strength as compared to healthy individuals. PMID:22606051
Shin, Dongyun; Kim, Hee Joo; Kim, Dae Suk; Kim, Soo Min; Park, Jin Su; Park, Yong-Beom; Lee, Min-Geol
The prevalence and clinical features of psoriatic arthritis (PsA) in psoriasis patients vary widely in different countries, and studies on Korean population are rarely reported. The aim of this study was to investigate the clinical features of PsA in a Korean population of patients with psoriasis by using psoriatic arthritis screening questionnaires. A cross-sectional observational study was conducted, and consecutive psoriatic patients were evaluated for PsA by using two kinds of psoriatic arthritis screening questionnaires: Psoriatic Arthritis Screening and Evaluation tool (PASE) and Psoriasis Epidemiology Screening Tool (PEST). Psoriatic patients with higher score in screening questionnaires were referred to rheumatologist for confirmative diagnosis of PsA. Among 196 psoriasis patients screened by PASE and PEST, total prevalence of PsA was 11.2 % (n = 22/196) with 59.1 % of the cases being newly diagnosed. Compared with patients without PsA, patients with PsA had more extensive psoriasis, higher frequency of pustular and inverse type of psoriasis, and lower frequency of plaque type of psoriasis. Spondylitis was the most common manifestation pattern, followed by polyarthritis, oligoarthritis, predominant distal interphalangeal arthritis, and arthritis mutilans. Our findings are consistent with a low prevalence of PsA among patients with psoriasis in Asia. We also confirm a spondylitis as the most common pattern of PsA in Korea. PsA screening questionnaires can be a simple and useful tool to screen PsA in patients with psoriasis.
Tey, Hong Liang; Ee, Hock Leong; Tan, Andy S L; Theng, Thiam Seng; Wong, Su Ni; Khoo, Shih Wee
The aim of this study was to determine if the following characteristics were associated with the presence of psoriatic arthritis in a sample of psoriasis patients: race, family history of psoriasis and psoriatic arthritis, age of onset of psoriasis, smoking, alcohol consumption and the maximum body surface area (BSA) affected by psoriasis. This was a case-control study involving 400 psoriasis patients who attended the Psoriasis and Photo-medicine clinic in the National Skin Center of Singapore over a 1-year period. Cases were psoriasis patients with psoriatic arthritis while controls were psoriasis patients without psoriatic arthritis. The diagnosis of psoriatic arthritis was made by rheumatologists and participants completed a self-administered standardized questionnaire. The maximum BSA involved was determined from the case notes. Psoriatic arthritis was not significantly associated with sex, race, age of onset of psoriasis, a family history of psoriasis, smoking and alcohol consumption but was significantly associated with a family history of psoriatic arthritis (P < 0.001) and the maximum body surface involved (P = 0.05). Using multivariate analysis to control for variables, the presence of psoriatic arthritis was significantly associated with a family history of psoriatic arthritis (odds ratio [OR] = 20.5; 95% confidence interval [CI] = 2.49-169.10) and the maximum BSA involved (OR = 2.52; 95% CI = 1.33-4.75). Indian psoriatic patients were more likely to have psoriatic arthritis compared to the other races. A family history of psoriatic arthritis and a greater maximum body surface involved may be associated with having psoriatic arthritis in this study population of psoriasis patients.
Masuko, Kayo; Tohma, Shigeto; Matsui, Toshihiro
Various medications are used for the treatment of rheumatoid arthritis (RA). Food-drug interactions may occur with concomitant ingestion of particular food. For example, methotrexate (MTX), the anchor drug in the therapeutic strategy against RA, is an antifolate agent. Excessive presence or absence of dietary folic acid may regulate MTX metabolism, possibly leading to unexpected adverse reactions. In this review, we focus on MTX, isoniazide and calcineurin inhibitors, and the implications of potential food-drug reactions in rheumatology, suggesting the important role of nutritional evaluations in RA patients.
Bosworth, Ailsa; Cox, Maureen; O'Brien, Anne; Jones, Peter; Sargeant, Ify; Elliott, Alison; Bukhari, Marwan
Patient experience is not routinely measured in rheumatoid arthritis (RA) and no accepted standardised Patient Reported Experience Measures (PREM) tools currently exist. Commissioning for Quality in Rheumatoid Arthritis (CQRA) has developed, piloted and validated PREMs for RA and other rheumatic conditions. Focus groups were held with RA patients to identify key elements of the patient experience. These were mapped against the UK Department of Health Patient Experience Framework and a PREM questionnaire developed with questions specifically relating to RA and rheumatology services. The RA PREM was piloted and Cronbach's alpha used to assess internal consistency. The PREM was modified to capture experience of patients with other rheumatic conditions and further validated. Ten UK sites and 524 patients were included in the RA PREM pilot and validation analysis. The RA PREM reliably captured RA patient experience and had good construct validity. Cronbach's alpha within the multiquestion domains ranged from 0.61 to 0.90 and the percentage agreement ranged from 22.5% to 70.4% with overall care. The modified PREM was evaluated in 11 UK sites and 110 patients with a range of rheumatic conditions. Cronbach's alpha ranged from 0.76 to 0.91 and the percentage agreement similarly ranged from 70% to 90% with the question on overall care. The RA PREM and the modified PREM provide new valuable validated tools for capturing the patient experience in a range of rheumatic conditions. The RA PREM is currently being used in a UK National Clinical Audit of Rheumatoid and Early Inflammatory Arthritis.
Kim, H A; Bae, Y D; Seo, Y I
This study was conducted to assess the contents of Web-sourced arthritis information and to determine its influence on arthritis patients and medical practice in Korea. An electronic search was conducted using the word "arthritis". Web sites found in the Korean language were critically assessed according to authorship, the type of publication, contents, financial interests, and the type of financial interest. Questionnaire surveys of arthritis patients and rheumatologists were performed to appraise the impact of the arthritis information on the Web. Among 138 web sites retrieved, 18.8% were classified as advertisement and 44.9% as having financial interests, such as the promotion of products or services. Among 257 arthritis patients surveyed, 28% reported that they searched for arthritis information on the web, and the parameters significantly associated with Internet searching were a younger age, being employed, and having a higher income and a higher education. While the difference in ratings regarding the accuracy of Web-sourced arthritis information between physicians and patients was not significant, only 16.1% of physicians responded that their patients understand the Internet content accurately. Physicians also tended to reply more negatively about the contents and the influence of Web-sourced arthritis information than patients. Analysis of Korean arthritis web sites revealed many sites with financial interests. There was also a discrepancy found between patients and physicians regarding the impact of Web-sourced arthritis information on the doctor-patient relationship. Because the impact of the Internet on health care is expected to increase, physicians need to be prepared to help patients benefit from information obtained from the Internet.
Cantini, Fabrizio; Niccoli, Laura; Nannini, Carlotta; Cassarà, Emanuele; Kaloudi, Olga; Giulio Favalli, Ennio; Becciolini, Andrea; Biggioggero, Martina; Benucci, Maurizio; Li Gobbi, Francesca; Grossi, Valentina; Infantino, Maria; Meacci, Francesca; Manfredi, Mariangela; Guiducci, Serena; Bellando-Randone, Silvia; Matucci-Cerinic, Marco; Foti, Rosario; Di Gangi, Marcella; Mosca, Marta; Tani, Chiara; Palmieri, Fabrizio; Goletti, Delia
A multidisciplinary expert panel, the Italian board for the TAilored BIOlogic therapy (ITABIO), was constituted to formulate evidence-based decisional statements for the first-line tailored biologic therapy in patient with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). Systematic review of the literature to identify English-language articles on the variables influencing the first-line biologic choice, including the efficacy and safety of the drug, the route of administration, the availability of response predictor biomarkers, the need of monotherapy, the patient socio-economic status, lifestyle, cultural level, personality, fertility and childbearing potential in women, the presence of comorbidities, the host-related risk factors for infection and latent tuberculosis infection (LTBI) reactivation, the cardiovascular (CV) risk, and costs. Some variables, including the patients' preference, the indication for anti-TNF monotherapy in potential childbearing women, and the intravenous route with dose titration in obese subjects resulted valid for all the three rheumatic conditions. Further, evidence of a better cost-effectiveness profile for etanercept (ETN) and biosimilar infliximab (IFX) in RA was found. Any biologic may be employed in absence of choice driving factors in RA. Otherwise, a high infection risk or LTBI positivity drive the choice toward abatacept (ABA), tocilizumab (TCZ), or ETN. TCZ should be the first choice if monotherapy is required. High rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) titers should drive the choice toward TCZ or ABA, while in patients at high CVD risk anti-TNF choice, with preference for ETN, seems appropriate. Presence of anterior uveitis or inflammatory bowel disease drives the choice to monoclonal antibody anti-TNFs (MoAb anti-TNFs). In PsA, ustekinumab (UTK), and to a lesser extent ETN, represents the first choice in patients at high infection and TB risk. Anti-TNFs or
Giassi, Karina de Souza; Furlanetto, Vilson; Fialho, Sonia; Gomes Ribeiro, Giovana; Pereira, Ivânio Alves
The antagonists of tumour necrosis factor (anti-TNF) have been successfully used in several chronic inflammatory diseases such as Rheumatoid Arthritis (RA), but some studies have observed the development of infections by intracellular pathogens in patients using anti-TNF. We report a case of a female patient with previous diagnosis of RA for 16 years that used several disease-modifying anti-rheumatic drugs (DMARDs) that resulted in treatment failure, and then was treated with infliximab. After fifteen days of the second dose, the patient developed ventilatory-dependent chest pain, dry cough and dyspnea. She was hospitalized, and the diagnosis of pneumonia by Legionella pneumophila was confirmed by the presence of Legionella antigen in an urine test. TNF is an inflammatory cytokine that also acts inhibiting the bacterial growth of intracellular pathogens, and its inhibition seems to increase susceptibility to these infections in some patients.
Peluso, G; Bosello, S L; Gremese, E; Mirone, L; Di Gregorio, F; Di Molfetta, V; Pirronti, T; Ferraccioli, G
Three-dimensional (3D) volumetric ultrasonography (US) is an interesting tool that could improve the traditional approach to musculoskeletal US in rheumatology, due to its virtual operator independence and reduced examination time. The aim of this study was to investigate the performance of 3DUS in the detection of bone erosions in hand and wrist joints of early rheumatoid arthritis (ERA) patients, with computed tomography (CT) as the reference method. Twenty ERA patients without erosions on standard radiography of hands and wrists underwent 3DUS and CT evaluation of eleven joints: radiocarpal, intercarpal, ulnocarpal, second to fifth metacarpo-phalangeal (MCP), and second to fifth proximal interphalangeal (PIP) joints of dominant hand. Eleven (55.0%) patients were erosive with CT and ten of them were erosive also at 3DUS evaluation. In five patients, 3DUS identified cortical breaks that were not erosions at CT evaluation. Considering CT as the gold standard to identify erosive patients, the 3DUS sensitivity, specificity, PPV, and NPV were 0.9, 0.55, 0.71, and 0.83, respectively. A total of 32 erosions were detected with CT, 15 of them were also observed at the same sites with 3DUS, whereas 17 were not seen on 3DUS evaluation. The majority of these 3DUS false-negative erosions were in the wrist joints. Furthermore, 18 erosions recorded by 3DUS were false positive. The majority of these 3DUS false-positive erosions were located at PIP joints. This study underlines the limits of 3DUS in detecting individual bone erosion, mostly at the wrist, despite the good sensitivity in identifying erosive patients.
Matuszewska, Agnieszka; Szechiński, Jacek
Rheumatoid arthritis (RA) is progressive, chronic, autoimmune, systemic connective tissue disease. It affects 0,5-1% population. RA manifests as inflammation of symmetrical mainly small and medium joints with synovial hypertrophy, extra-articular lesions and systemic complications. Depending on intensity and duration of RA in imaging studies the patients demonstrate narrowing of articular fissures, presence of geodes, erosions, subluxations and/or synostoses. Progressive bone mass loss in the joint involved by the morbid process and in the entire skeleton was also described. Local (periarticular) osteoporosis is linked to the presence of cytokines and growth factors, which regulate reciprocal interactions between osteoclasts, osteoblasts and immune system cells. In the inflamed joint accumulate synoviocytes of fibroblast phenotype, synoviocytes of macrophage phenotype, antigen presenting cells, lymphocytes T, activated lymphocytes B, plasma cells and neutrophils. Increased expression of receptor activator of nuclear factor κB (RANKL), macrophage-colony stimulating factor (M-CSF), presence of TNFα, IL-1, IL-6, IL-7, IL-17 influences pathological loss of bone mass. Rheumatoid arthritis is an important risk factor of generalised osteoporosis and fractures, involved in FRAX (fracture risk assessment) algorythm. Generalised osteoporosis in patients with RA has a multifactorial aetiology. Its development reflects effects of both: factors linked to the disease (presence of proinflammatory cytokines, disability of the patients, applied therapy) and classical risk factors of osteoporosis (e.g. advanced age, sex, post-menopausal period, genetic predisposition, low peak bone mass, low body weight, deficiency of calcium and vitamin D, tobacco smoking).
Gherghe, Ana Maria; Dougados, Maxime; Combe, Bernard; Landewé, Robert; Mihai, Carina; Berenbaum, Francis; Mariette, Xavier; Wolterbeek, Ron; van der Heijde, Désirée
Objectives To investigate the prevalence of comorbidities in early rheumatoid arthritis (ERA) and early axial spondyloarthritis (ESpA) versus the general population. Methods Baseline data of 689 patients with ERA from the Etude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) cohort (age 48.2±12.1 years, symptoms duration 14.2±14.5 weeks) and 645 patients with ESpA from Devenir des Spondylarthropathies Indifférenciées Récentes (DESIR; age 32.8±8.4 years, axial symptoms duration 79.0±45.7 weeks) were analysed. Metabolic and cardiovascular diseases (CVD), infections and neoplasia were determined in each cohort. The prevalence (95% CI) of several comorbidities was compared with that in the French general population. For patients without CVD, the 10-year risk of developing CVD was calculated using the Framingham and SCORE equations. The heart age was calculated using the 2008 Framingham points system. Results 42% of patients with ERA and 20.3% of patients with ESpA had at least 1 comorbidity; the most common were arterial hypertension (AHT) and dyslipidaemia. AHT prevalence (95% CI) in ERA (18.2% (15.5% to 21.3%)), but not in ESpA (5.08% (3.57% to 7.14%)), was significantly increased (p<0.05) compared with the general population (7.58%). Prevalence of tuberculosis history was higher in ERA (4.7% (3.3% to 6.6%)), and ESpA (0.99% (0.4% to 2.3%)) than in the general population (0.02%; both p<0.05). No differences were observed in malignancies, coronary heart disease or diabetes. In ERA, among patients without a history of CVD, an intermediate to high CVD risk was found. The heart age exceeded the real age by 4.1±9.6 years in ERA and by 2.1±7.0 years in ESpA (p<0.001). Conclusions We found an increased prevalence of AHT and tuberculosis history in ERA and ESpA, and an increased CVD risk. These results should prompt rheumatologists to check these comorbidities early in the disease. PMID:26535145
Describes a study undertaken to ascertain the extent to which arthritis patients could be targeted by arthritis-related programming over a local cable system. Some conceptual and practical issues involved in targeting chronic patient groups for health programming are discussed. (Author/CT)
Mittal, Manoj; Hassan, Basit; Desai, Khushboo; Duseja, Shilpa; Kumar, Santosh; Reddy, Sharaschandra G
The associational studies between periodontitis and rheumatoid arthritis are less documented, although they are found to have similar inflammatory pathogenesis. Resistin, a novel adipokine is suggested to be a common link between periodontitis and rheumatoid arthritis. The aim of the present study was to reinforce the inter-relationship between periodontitis and rheumatoid arthritis by using resistin as a potent inflammatory marker. Hundred patients (aged >30 y) of either sex were selected for this study and were divided equally into four groups of 25 patients each. Group A consisted of healthy individuals, Group B consisted of patients with chronic periodontitis, Group C of patients with rheumatoid arthritis and Group D had patients suffering from both arthritis and periodontitis. Periodontal parameters assessed were plaque index (PI), modified gingival index (GI) and probing depth (PD). Panoramic radiographs were taken to confirm the diagnosis of periodontitis. Rheumatoid arthritis was confirmed by the rheumatologists and seropositivity for rheumatoid factor (RF) was checked. Resistin levels were analysed in GCF collected from all the four groups and statistical analysis was done by using Pearson correlation coefficient. The GCF of all the patients showed presence of resistin. The level of resistin was highest in Group D patients and least in Group A patients. On analysing the samples together positive co-relation was found between GCF resistin and PD, PI, GI and RF. Resistin levels are increased in both chronic periodontitis and rheumatoid arthritis. Therefore, the increased level of GCF resistin can be regarded as potential inflammatory marker for periodontitis and rheumatoid arthritis.
Describes a study undertaken to ascertain the extent to which arthritis patients could be targeted by arthritis-related programming over a local cable system. Some conceptual and practical issues involved in targeting chronic patient groups for health programming are discussed. (Author/CT)
Allam, Riham S. H. M.; Abd-Elmohsen, Mai N.; Khafagy, Mohamed M.; Raafat, Karim A.; Sheta, Sherif M.
Purpose. To evaluate the role of spectral-domain optical coherence tomography (SD-OCT) in early detection of Chloroquine maculopathy in rheumatoid arthritis (RA) patients. Methods. 40 left eyes of 40 female rheumatoid arthritis patients who received treatment chloroquine for more than one year were recruited in the study. All patients had no symptoms or signs of Chloroquine retinopathy. They were evaluated using SD-OCT, where the Central Foveal Thickness (CFT), parafoveal thickness and perifoveal thickness, average Retinal Nerve Fiber Layer (RNFL) thickness, and Ganglion Cell Complex (GCC) measurements were measured and compared to 40 left eyes of 40 normal females. Results. The mean CFT was found to be thinner in the Chloroquine group (238.15 µm ± 22.49) than the normal controls (248.2 µm ± 19.04), which was statistically significant (p value = 0.034). The mean parafoveal thickness was lesser in the Chloroquine group than the control group in all quadrants (p value <0.05). The perifoveal thickness in both groups showed no statistically significant difference (p value >0.05) in all quadrants. No significant difference was detected between the two groups regarding RNFL, GCC, or IS/OS junction. Conclusions. Preclinical Chloroquine toxicity can lead to early thinning in the central fovea as well as the parafoveal regions that is detected by SD-OCT. PMID:26301102
Peluso, Rosario; Cafaro, Giovanni; Di Minno, Alessandro; Iervolino, Salvatore; Ambrosino, Pasquale; Lupoli, Gelsy; Di Minno, Matteo Nicola Dario
Psoriatic arthritis is an inflammatory rheumatic disorder, which occurs in patients with skin and/or nail psoriasis. In psoriatic arthritis, the importance of biologic mediators modulating inflammatory reaction, such as tumor necrosis factor, and the knowledge on their role in the pathogenesis of psoriatic arthritis influence the therapeutic choices. In the last years, the introduction of biologic drugs has greatly changed the treatment of psoriasis and psoriatic arthritis. In fact, tumor necrosis factor-α blockers demonstrated an effective action in the treatment of both skin and joint manifestations of psoriatic arthritis, but they have some adverse effects. The aim of this review is to revisit the literature data on adverse effects of tumor necrosis factor-α blockers in patients with psoriatic arthritis.
Burmester, Gerd R; Rigby, William F; van Vollenhoven, Ronald F; Rubbert-Roth, Andrea; Kelman, Ariella; Dimonaco, Sophie; Mitchell, Nina
Objectives The efficacy of tocilizumab (TCZ), an anti-interleukin-6 receptor antibody, has not previously been evaluated in a population consisting exclusively of patients with early rheumatoid arthritis (RA). Methods In a double-blind randomised controlled trial (FUNCTION), 1162 methotrexate (MTX)-naive patients with early progressive RA were randomly assigned (1:1:1:1) to one of four treatment groups: 4 mg/kg TCZ+MTX, 8 mg/kg TCZ+MTX, 8 mg/kg TCZ+placebo and placebo+MTX (comparator group). The primary outcome was remission according to Disease Activity Score using 28 joints (DAS28–erythrocyte sedimentation rate (ESR) <2.6) at week 24. Radiographic and physical function outcomes were also evaluated. We report results through week 52. Results The intent-to-treat population included 1157 patients. Significantly more patients receiving 8 mg/kg TCZ+MTX and 8 mg/kg TCZ+placebo than receiving placebo+MTX achieved DAS28-ESR remission at week 24 (45% and 39% vs 15%; p<0.0001). The 8 mg/kg TCZ+MTX group also achieved significantly greater improvement in radiographic disease progression and physical function at week 52 than did patients treated with placebo+MTX (mean change from baseline in van der Heijde–modified total Sharp score, 0.08 vs 1.14 (p=0.0001); mean reduction in Health Assessment Disability Index, −0.81 vs −0.64 (p=0.0024)). In addition, the 8 mg/kg TCZ+placebo and 4 mg/kg TCZ+MTX groups demonstrated clinical efficacy that was at least as effective as MTX for these key secondary endpoints. Serious adverse events were similar among treatment groups. Adverse events resulting in premature withdrawal occurred in 20% of patients in the 8 mg/kg TCZ+MTX group. Conclusions TCZ is effective in combination with MTX and as monotherapy for the treatment of patients with early RA. Trial registration number ClinicalTrials.gov, number NCT01007435 PMID:26511996
Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naïve patients with early, active rheumatoid arthritis with poor prognostic factors: 1-year results from C-EARLY, a randomised, double-blind, placebo-controlled phase III study
Emery, P; Bingham, C O; Burmester, G R; Bykerk, V P; Furst, D E; Mariette, X; van Vollenhoven, R; Arendt, C; Mountian, I; Purcaru, O; Tatla, D; VanLunen, B; Weinblatt, M E
Objectives To assess the efficacy and safety of certolizumab pegol (CZP)+dose-optimised methotrexate (MTX) versus placebo (PBO)+dose-optimised MTX in inducing and sustaining clinical remission in DMARD-naïve patients with moderate-to-severe, active, progressive rheumatoid arthritis (RA), with poor prognostic factors over 52 weeks. Methods DMARD-naïve patients with ≤1 year of active RA were randomised (3:1) in a double-blind manner to CZP (400 mg Weeks 0, 2, 4, then 200 mg Q2W to Week 52)+MTX or PBO+MTX (the mean optimised-MTX dose=21 and 22 mg/week, respectively). Sustained remission (sREM) and sustained low disease activity (sLDA; DAS28(ESR)<2.6 and DAS28(ESR)≤3.2, respectively, at both Weeks 40 and 52) were the primary and secondary endpoints. Results Patients were randomised to CZP+MTX (n=660) and PBO+MTX (n=219). At Week 52, significantly more patients assigned to CZP+MTX compared with PBO+MTX achieved sREM (28.9% vs 15.0%, p<0.001) and sLDA (43.8% vs 28.6%, p<0.001). Inhibition of radiographic progression and improvements in physical functioning were significantly greater for CZP+MTX versus PBO+MTX (van der Heijde modified total Sharp score (mTSS) mean absolute change from baseline (CFB): 0.2 vs 1.8, p<0.001, rate of mTSS non-progressors: 70.3% vs 49.7%, p<0.001; least squares (LS) mean CFB in Health Assessment Questionnaire-Disability Index (HAQ-DI): −1.00 vs −0.82, p<0.001). Incidence of adverse events (AEs) and serious AEs was similar between treatment groups. Infection was the most frequent AE, with higher incidence for CZP+MTX (71.8/100 patient-years (PY)) versus PBO+MTX (52.7/100 PY); the rate of serious infection was similar between CZP+MTX (3.3/100 PY) and PBO+MTX (3.7/100 PY). Conclusions CZP+dose-optimised MTX treatment of DMARD-naïve early RA resulted in significantly more patients achieving sREM and sLDA, improved physical function and inhibited structural damage compared with PBO+dose-optimised MTX. Trial registration
Faria, A D; Lopes, A J; Jansen, J M; Pinheiro, G C; Melo, P L
The objective of this study was to evaluate the clinical potential of the Forced Oscillation Technique (FOT) in the detection of the early alterations in respiratory mechanics of Rheumatoid Arthritis (RA) patients. A total of 36 individuals were analyzed, 18 healthy and 18 with RA. The clinical usefulness of the parameters was evaluated investigating sensibility (Se), specificity (Sp) and the area under the receiver operating characteristic curve (AUC). In the RA group, all the 3 studied parameters obtained high accuracy for clinical use (AUC>0.9), while in spirometric parameters, no parameter obtained appropriate accuracy for clinical use (AUC < 0.7). In conclusion, the parameters obtained by FOT presented adequate Se and Sp, indicating that this technique can be helpful in the evaluation of the early respiratory mechanical alterations in patients with RA.
Withrington, R H; Teitsson, I; Valdimarsson, H; Seifert, M H
Thirty-three patients with early peripheral synovitis were followed up for two to four years in order to study the relationship between fluctuations in rheumatoid factor (RF) levels and indices of clinical activity. Twenty-eight of these patients developed classical/definite rheumatoid arthritis (RA). Seventeen patients developed erosive disease of their hands and wrists and thirteen had a positive RF agglutination test. Nineteen patients had raised levels of IgM, RF, IgA, RF, or IgG RF as measured by isotype-specific ELISA techniques. The within-patient fluctuations in IgA RF levels correlated significantly with the corresponding fluctuations in grip strength (p less than 0.05), erythrocyte sedimentation rate (ESR) (p less than 0.01), and a composite index of disease activity (p less than 0.02). IgG RF levels were also associated with changes in ESR and grip strength, but IgM RF showed only a weak association with fluctuations in ESR and not with any other clinical parameters. It is suggested that serum IgA RF may be a useful marker of disease activity in rheumatoid arthritis. PMID:6497460
Denys, Anne; Clavel, Gaëlle; Lemeiter, Delphine; Schischmanoff, Olivier; Boissier, Marie-Christophe; Semerano, Luca
Cardiovascular disease (CVD) is a major cause of morbidity and mortality in rheumatoid arthritis (RA). There are limited experimental data on vascular involvement in arthritis models. To study the link between CVD and inflammation in RA, we developed a model of vascular dysfunction and articular inflammation by collagen-induced arthritis (CIA) in C57Bl/6 (B6) mice. We studied the expression of vascular inflammatory markers in CIA with and without concomitant hyperlipidic diet (HD). Collagen-induced arthritis was induced with intradermal injection of chicken type-II collagen followed by a boost 21 days later. Mice with and without CIA were fed a standard diet or an HD for 12 weeks starting from the day of the boost. Arthritis severity was evaluated with a validated clinical score. Aortic mRNA levels of vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS) and interleukin-17 were analysed by quantitative RT-PCR. Vascular cell adhesion molecule-1 localization in the aortic sinus was determined by immunohistochemistry. Atherosclerotic plaque presence was assessed in aortas. Collagen-induced arthritis was associated with increased expression of VCAM-1, independent of diet. VCAM-1 overexpression was detectable as early as 4 weeks after collagen immunization and persisted after 15 weeks. The HD induced atheroma plaque formation and aortic iNOS expression regardless of CIA. Concomitant CIA and HD had no additive effect on atheroma or VCAM-1 or iNOS expression. CIA and an HD diet induced a distinct and independent expression of large-vessel inflammation markers in B6 mice. This model may be relevant for the study of CVD in RA.
Batún Garrido, José Antonio de Jesús; Olán, Francisco; Hernández Núñez, Éufrates
Dyslipidaemia is one of the main risk factors for atherosclerotic cardiovascular disease. Patients with rheumatoid arthritis have 2-3 times more cardiovascular risk, which is partly due to the pattern of lipids which increase the atherogenic index. A descriptive, cross-sectional, observational and prospective study was conducted on 82 patients, selected for their lipid profile. Variables associated with the disease and the drugs used were recorded. Atherogenic risk was calculated, with Chi square being used for categorical variables, and the Mann-Whitney test for the continuous ones. The dyslipidaemia frequency was 54.9%. The most frequent age range of dyslipidaemia was between 51 and 60 years. Patients with type i obesity had a higher frequency of dyslipidaemia. Less dyslipidaemia was found with a lower rate of disease activity. Patients with cyclic citrullinated anti-peptide antibodies and positive rheumatoid factor, erythrocyte sedimentation rate>13mm or CRP>2mg/L had a higher frequency of dyslipidaemia. The mean Castelli atherogenic index was 4.36, the index of Kannel was 2.59, and triglycerides/HDL-c ratio was 3.83.Patients with dyslipidaemia showed a higher frequency of positive rheumatoid factor (P=.0008), and those patients who were taking hydroxychloroquine had a lower frequency of dyslipidaemia P=.03. Patients with rheumatoid arthritis have a pro-atherogenic lipid profile. It is important to know this and treat it to reduce cardiovascular risk. Copyright © 2016 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.
Kulshrestha, Vikas; Datta, Barun; Kumar, Santhosh; Mittal, Gaurav
With increasing number of patients with early osteoarthritis of knee opting for total knee arthroplasty (TKA), there has been increase in patients dissatisfied with surgical outcomes. It is being presumed that offering unicondylar knee arthroplasty (UKA) to them would improve outcomes. Primary objective of our study was to look for any difference in patient-reported outcome and function at 2-year follow-up in patients undergoing UKA as compared to TKA. Our study was a randomized study with parallel assignment conducted at a high-volume specialized arthroplasty center. Eighty patients with bilateral isolated medial compartment knee arthritis were randomized into simultaneous 2-team bilateral TKA (n = 40) and UKA (n = 40) group. We finally analyzed 36 patients in each group. Main outcome measure was improvement in Knee Outcome Survey-Activities of Daily Living Scale (KOS-ADLS) and High Activity Arthroplasty Score (HAAS) obtained at 2-year follow-up. Improvement in KOS-ADLS and HAAS at 2 years was similar (P = .2143 and .2010) in both groups. Performance as assessed with Delaware index was also similar. Length of hospital stay was less in UKA group (6.6 days as against 5.4 days). Complications and readmission rates were more in TKA group (nil in UKA group; 08 in TKA group). At 2-year follow-up, UKA provides similar improvement in patient-reported outcomes, function, and performance as compared to TKA when performed in patients with early arthritis. However, UKA patients have shorter hospital stay and fewer complications. Copyright © 2016 Elsevier Inc. All rights reserved.
Verhoeven, A; Boers, M; van der Linden, S
OBJECTIVE—Validation of responsiveness and discriminative power of the World Health Organisation/International League of Associations for Rheumatology (WHO/ILAR) core set, the American College of Rheumatology (ACR), and European League for Rheumatology (EULAR) criteria for improvement/response, and other single and combined measures (indices) in a trial in patients with early rheumatoid arthritis (RA). METHODS—Ranking of measures by response (standardised response means and effect sizes) and between-group discrimination (unpaired t test and χ2 values) at two time points in the COBRA study. This study included 155 patients with early RA randomly allocated to two treatment groups with distinct levels of expected response: combined treatment, high response; sulfasalazine treatment, moderate response. RESULTS—At week 16, standardised response means of core set measures ranged between 0.8 and 3.5 for combined treatment and between 0.4 and 1.2 for sulfasalazine treatment (95% confidence interval ±0.25). Performance of patient oriented measures (for example, pain, global assessment) was best when the questions were focused on the disease. The most responsive single measure was the patient's assessment of change in disease activity, at 3.5. Patient utility, a generic health status measure, was moderately (rating scale) to poorly (standard gamble) responsive. Response means of most indices (combined measures) exceeded 2.0, the simple count of core set measures improved by 20% was most responsive at 4.1. Discrimination performance yielded similar but not identical results: best discrimination between treatment groups was achieved by the EULAR response and ACR improvement criteria (at 20% and other percentage levels), the pooled index, and the disease activity score (DAS), but also by the Health Assessment Questionnaire (HAQ) and grip strength. CONCLUSIONS—Responsiveness and discrimination between levels of response are not identical concepts, and
Masoud, Sherry; Lim, Phang Boon; Kitas, George D; Panoulas, Vasileios
An increased cardiovascular morbidity and mortality, including the risk of sudden cardiac death (SCD), has been shown in patients with rheumatoid arthritis (RA). Abnormalities in autonomic markers such as heart rate variability and ventricular repolarization parameters, such as QTc interval and QT dispersion, have been associated with sudden death in patients with RA. The interplay between these parameters and inflammation that is known to exist with RA is of growing interest. In this article, we review the prevalence and predictors of SCD in patients with RA and describe the potential underlying mechanisms, which may contribute to this. We also review the impact of biologic agents on arrhythmic risk as well as cardiovascular morbidity and mortality. PMID:28824786
Rasch, Linda A; van Tuyl, Lilian H D; Lems, Willem F; Boers, Maarten
Treatment with initial high-dose prednisolone and a combination of methotrexate (MTX) and sulfasalazine (SSZ) according to the COBRA regimen (Dutch acronym for combinatietherapie bij reumatoide artritis, 'combination therapy for rheumatoid arthritis'), has repeatedly been demonstrated to be very effective in early rheumatoid arthritis (RA). COBRA combination therapy is superior to initial monotherapy of SSZ and MTX, is also associated with a good long-term outcome, is as safe as other treatment regimes, and performs as well as the combination of high-dose MTX and the tumor necrosis factor antagonist infliximab. A pilot study with an intensified version of the COBRA combination therapy showed that strict monitoring and aggressive treatment intensification based on the Disease Activity Score can result in a remission rate of 90% in patients with active early RA. Also, the first results indicate that an attenuated variation on COBRA combination therapy, called 'COBRA-light', is effective in decreasing disease activity and is generally well tolerated. Based on these results, we conclude that initial high-dose prednisolone in combination with MTX and SSZ could or should be the first choice in early active RA since it is effective and safe, and the cost price of the drugs is low. © 2014 S. Karger AG, Basel.
Aira, Lazaro E.; Hernández, Patricia; Prada, Dinorah; Chico, Araceli; Gómez, Jorge A.; González, Zuyén; Fuentes, Karla; Viada, Carmen; Mazorra, Zaima
Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation that affects approximately 1% of the general population. Itolizumab, a monoclonal antibody specific for the human CD6 molecule mainly expressed on T lymphocytes, has been shown to inhibit proliferation of T cells and proinflammatory cytokine production in psoriasis patients. We have now assessed the immunological effect of itolizumab in combination with methotrexate in rheumatoid arthritis by analyzing clinical samples taken from 30 patients enrolled in a clinical trial. T and B cell subpopulations were measured at different time points of the study. Plasma cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. The combined treatment of itolizumab and methotrexate led to a reduction in the frequency of T cell subpopulations, and plasma levels of proinflammatory cytokines showed a significant decrease up to at least 12 weeks after treatment ended. No anti-idiotypic antibody response was detected. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease. PMID:26466969
Aira, Lazaro E; Hernández, Patricia; Prada, Dinorah; Chico, Araceli; Gómez, Jorge A; González, Zuyén; Fuentes, Karla; Viada, Carmen; Mazorra, Zaima
Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation that affects approximately 1% of the general population. Itolizumab, a monoclonal antibody specific for the human CD6 molecule mainly expressed on T lymphocytes, has been shown to inhibit proliferation of T cells and proinflammatory cytokine production in psoriasis patients. We have now assessed the immunological effect of itolizumab in combination with methotrexate in rheumatoid arthritis by analyzing clinical samples taken from 30 patients enrolled in a clinical trial. T and B cell subpopulations were measured at different time points of the study. Plasma cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. The combined treatment of itolizumab and methotrexate led to a reduction in the frequency of T cell subpopulations, and plasma levels of proinflammatory cytokines showed a significant decrease up to at least 12 weeks after treatment ended. No anti-idiotypic antibody response was detected. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease.
Luime, Jolanda J; Buisman, Leander R; Oppe, Mark; Hazes, Johanna M W; Rutten-van Mölken, Maureen P M H
New opportunities have emerged for early diagnosis with the arrival of new technologies that assess the impact of genomics, proteomics, metabolomics, and cytomics on rheumatoid arthritis (RA) risk. This early health technology assessment study assesses the short-term cost effectiveness of 4 add-on diagnostic tests in early inflammatory arthritis patients at risk of RA. We modeled 4 diagnostic add-on tests to the American College of Rheumatology/European League Against Rheumatism 2010 RA classification criteria, covering the first year after diagnosis, using Rotterdam Early Arthritis Cohort data. Sensitivity, specificity, and costs were assigned to the magnetic resonance imaging of hands and feet (sensitivity 0.90, specificity 0.60, cost €756), interleukin-6 (IL-6) serum level test (sensitivity 0.70, specificity 0.53, cost €50), B cell-related gene expression (sensitivity 0.60, specificity 0.90, cost €150), and gene assay for RA (sensitivity 0.40, specificity 0.85, cost €750), based on literature and expert opinion. Outcomes were evaluated using the unweighted diagnostic net benefit (UDNB) and the incremental cost-effectiveness ratio (ICER) in all patients (n = 552), intermediate-risk patients (n = 263), and seronegative patients (n = 329). The highest UDNB was found when using the B cell assay in intermediate-risk patients (43%, ICER €5,314), while the IL-6 test in seronegative patients resulted in the lowest UDNB (-11.4%, ICER €7,650). If a threshold of €20,000 is applied, the B cell assay would be preferred over the other alternatives, with a 78% probability of being cost effective for intermediate-risk patients, 57% for all patients, and 73% for seronegative patients. Diagnostic add-on tests favoring specificity over sensitivity with a headroom less than €370 per test are cost effective, with the largest diagnostic benefit occurring in intermediate-risk patients. © 2016, American College of Rheumatology.
Curtis, JR; Yang, S; Chen, L; Pope, JE; Keystone, EC; Haraoui, B; Boire, G; Thorne, JC; Tin, D; Hitchon, CA; Bingham, CO; Bykerk, VP
Background Simplified measures to quantify rheumatoid arthritis (RA) disease activity are increasingly used. The minimally clinically important differences (MCID) for some measures, such as the clinical disease activity index (CDAI), have not been well-defined in real-world clinic settings, especially for early RA patients with low/moderate disease activity. Methods Data from Canadian Early Arthritis Cohort patients were used to examine absolute change in CDAI in the first year after enrollment, stratified by disease activity. MCID cutpoints were derived to optimize the sum of sensitivity and specificity versus the gold standard of patient self-reported improvement or worsening. Specificity, positive predictive value and negative predictive values were calculated against patient self-reported improvement (gold standard) and for change in pain, HAQ and DAS28 improvement. Discrimination was examined using area under receiver operator curves (ROC). Similar methods were used to evaluate MCIDs for worsening for patients who achieved low disease activity. Results A total of 578 patients (mean (SD) age 54.1 (15.3) years; 75% women, median (IQR) disease duration 5.3 (3.3, 8.0) months) contributed 1169 visit pairs to the improvement analysis. The MCID cutpoints for improvement were 12 (patients starting in high disease activity, CDAI>22), 6 (moderate, CDAI 10–22), and 1 (low disease activity, CDAI <10). Performance characteristics were acceptable using these cutpoints for pain, HAQ, and DAS28. The MCID for CDAI worsening among patients who achieved low disease activity was 2 units. Conclusions These minimally important absolute differences in CDAI can be used to evaluate improvement and worsening and increase the utility of CDAI in clinical practice. PMID:25988705
Choi, In Ah; Kim, Jin-Hee; Kim, Yong Mi; Lee, Joo Youn; Kim, Kyung Hwa; Lee, Eun Young; Lee, Eun Bong; Lee, Yong-Moo; Song, Yeong Wook
A cross-sectional study was undertaken to investigate the association between severity of periodontitis and clinical manifestation of rheumatoid arthritis (RA). Two hundred sixty-four RA patients and 88 age- and sex-matched controls underwent dental exam. Additionally, clinical manifestations including disease activity and anti-citrullinated protein antibodies were evaluated in RA patients. The prevalence of moderate or severe periodontitis was higher in RA patients compared to controls (63.6% vs 34.1%, p < 0.001). In markers of periodontal inflammation, bleeding on probing was correlated with disease activity score 28 (r = 0.128, p = 0.041), RA disease duration (r = 0.211, p = 0.001), erythrocyte sedimentation rate (ESR; r = 0.141, p = 0.023), anti-cyclic citrullinated peptide antibody (r = 0.183, p = 0.009), and anti-citrullinated α-enolase peptide-1 antibody (r = 0.143, p = 0.025). Gingival index was correlated with RA duration (r = 0.262, p < 0.001), ESR (r = 0.162, p = 0.009), anti-cyclic citrullinated peptide antibody (r = 0.203, p = 0.004) and anti-citrullinated α-enolase peptide-1 antibody (r = 0.225, p < 0.001). Periodontal structural damage represented by probing pocket depth and clinical attachment level were less in RA patients with human leukocyte antigen (HLA)-DRB1 shared epitope compared than those without shared epitope (p = 0.005 and p =0.006, respectively). The prevalence of moderate or severe periodontitis was increased in RA patients compared to controls. Periodontal inflammation was correlated with RA disease duration, ESR, and anti-citrullinated protein antibodies. Periodontal structural damage was less in RA patients with HLA-DRB1 shared epitope.
Choi, In Ah; Kim, Jin-Hee; Kim, Yong Mi; Lee, Joo Youn; Kim, Kyung Hwa; Lee, Eun Young; Lee, Eun Bong; Lee, Yong-Moo; Song, Yeong Wook
Background/Aims: A cross-sectional study was undertaken to investigate the association between severity of periodontitis and clinical manifestation of rheumatoid arthritis (RA). Methods: Two hundred sixty-four RA patients and 88 age- and sex-matched controls underwent dental exam. Additionally, clinical manifestations including disease activity and anti-citrullinated protein antibodies were evaluated in RA patients. Results: The prevalence of moderate or severe periodontitis was higher in RA patients compared to controls (63.6% vs 34.1%, p < 0.001). In markers of periodontal inflammation, bleeding on probing was correlated with disease activity score 28 (r = 0.128, p = 0.041), RA disease duration (r = 0.211, p = 0.001), erythrocyte sedimentation rate (ESR; r = 0.141, p = 0.023), anti-cyclic citrullinated peptide antibody (r = 0.183, p = 0.009), and anti-citrullinated α-enolase peptide-1 antibody (r = 0.143, p = 0.025). Gingival index was correlated with RA duration (r = 0.262, p < 0.001), ESR (r = 0.162, p = 0.009), anti-cyclic citrullinated peptide antibody (r = 0.203, p = 0.004) and anti-citrullinated α-enolase peptide-1 antibody (r = 0.225, p < 0.001). Periodontal structural damage represented by probing pocket depth and clinical attachment level were less in RA patients with human leukocyte antigen (HLA)-DRB1 shared epitope compared than those without shared epitope (p = 0.005 and p =0.006, respectively). Conclusions: The prevalence of moderate or severe periodontitis was increased in RA patients compared to controls. Periodontal inflammation was correlated with RA disease duration, ESR, and anti-citrullinated protein antibodies. Periodontal structural damage was less in RA patients with HLA-DRB1 shared epitope. PMID:27017391
Renato, Guzman M
Rheumatoid arthritis is a severe, aggressive, and debilitating disease that has a high mortality rate. There have been considerable advances in the last few years as a result of developments in molecular biology, immunology, and biotechnology. The knowledge about the elements that directly participate in the genesis of the disease has been established. Nowadays, treatments are more rational and are directed to specific targets. Anticytokine agents, especially therapies that target tumor necrosis factor (TNF), are considered to be frontline biological agents for the treatment of rheumatoid arthritis. The blocking of lymphocyte B with rituximab, a genetically engineered chimerical monoclonal antibody, has been approved by the US Food and Drug Administration as a treatment in patients with rheumatoid arthritis who have severe disease not responding to conventional multiple therapies and to TNF-blocker agents. We propose that patients with severe aggressive rheumatoid arthritis could benefit from rituximab without previous exposure to anti-TNF agents as a biological agent, and we postulate that rituximab could be used as a first-line biological agent in this subgroup. We present our recent experience with patients having severe and active rheumatoid disease with whom we used rituximab as a first-line biological agent.
Introduction Juvenile idiopathic arthritis (JIA) is the most common rheumatological disease of childhood with a prevalence of around 1 in 1,000. Without appropriate treatment it can have devastating consequences including permanent disability from joint destruction and growth deformities. Disease aetiology remains unknown. Investigation of disease pathology at the level of the synovial membrane is required if we want to begin to understand the disease at the molecular and biochemical level. The synovial membrane proteome from early disease-stage, treatment naive JIA patients was compared between polyarticular and oligoarticular subgroups. Methods Protein was extracted from 15 newly diagnosed, treatment naive JIA synovial membrane biopsies and separated by two dimensional fluorescent difference in-gel electrophoresis. Proteins displaying a two-fold or greater change in expression levels between the two subgroups were identified by matrix assisted laser desorption ionization-time of flight mass spectrometry with expression further verified by Western blotting and immunohistochemistry. Results Analysis of variance analysis (P ≤ 0.05) revealed 25 protein spots with a two-fold or greater difference in expression levels between polyarticular and oligoarticular patients. Hierarchical cluster analysis with Pearson ranked correlation revealed two distinctive clusters of proteins. Some of the proteins that were differentially expressed included: integrin alpha 2b (P = 0.04); fibrinogen D fragment (P = 0.005); collagen type VI (P = 0.03); fibrinogen gamma chain (P = 0.05) and peroxiredoxin 2 (P = 0.02). The identified proteins are involved in a number of different processes including platelet activation and the coagulation system. Conclusions The data indicate distinct synovial membrane proteome profiles between JIA subgroups at an early stage in the disease process. The identified proteins also provide insight into differentially perturbed pathways
Viton, J M; Atlani, L; Mesure, S; Franceschi, J P; Massion, J; Delarque, A; Bardot, A
The purpose of this study was to identify changes in equilibrium and movement control strategies in patients with arthritis of the knee. These strategies were expected to be different from those of healthy subjects because of the impairments caused by knee arthritis. The different phases of a side step were studied in patients with severe knee arthritis using a movement analysis system and force-plates. The duration of the postural phase and the intensity of the horizontal ground reaction forces during the postural phase were increased when the pathological limb was the supporting one. The monopodal phase was shortened on the pathological leg. These results show that knee arthritis patients develop new posturomotor strategies mainly aimed at shortening the monopodal phase when the affected leg is the supporting one. This movement analysis method enables quantification of differences that cannot be observed on clinical examination between knee arthritis patients and control subjects, and provides additional information to the usual clinical evaluation scales.
Mosleh-shirazi, Mohammad Saeed; Ibrahim, Mazin; Pastides, Philip; Rahman, Habib
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. PMID:26236339
Mendes, Maiana Darwich; Cavallo, Rafael Ruiz; Carvalhães, Cecilia Helena Vieira Franco Godoy; Ferrarini, Maria Aparecida Gadiani
To report a case septic arthritis with a rare pathogen in a immunosuppressed child. Male patient, 6 years old, had liver transplant 5 and half years ago due to biliary atresia. Patient was using tacrolimus 1mg q.12hours. This patient started to have pain in left foot and ankle and had one episode of fever 3 days before hospital admission. Physical Examination showed weight 17kg, height 109cm, temperature 36,4°C, with pain, swelling and heat in the left ankle, without other clinical signs. Initial tests: hemoglobin 11,7g/dL hematocrit 36.4%, leukocyte count 17600/uL (7% banded neutrophils, 70% segmented neutrophils, 2% eosinophils, basophils 1%, 13% lymphocytes, 7% monocytes) C-reactive protein 170,88mg/L. Joint ultrasound showed moderate effusion in the site. Patient was submitted to surgical procedure and S. multivorum was isolated from the effusion. The germ was susceptible to broad spectrum cephalosporins (ceftriaxone and cefepime) and fluoroquinolones (ciprofloxacin and levofloxacin), and it was resistant to carbapenemic antibiotics and aminoglycosides. He was treated intravenously with oxacillin for 15 days and ceftriaxone for 13 days, and orally with ciprofloxacin for 15 days, with good outcome. The Sphingobacterium multivorum is a gram negative bacillus that belongs to Flavobacteriaceae family and it is considered non-pathogenic. It has rarely been described as a cause of infections in humans, especially in hospital environment and in immunosuppressed patients. This case report is relevant for its unusual etiology and for the site affected, which may be the first case of septic arthritis described. Copyright © 2016 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.
Mendes, Maiana Darwich; Cavallo, Rafael Ruiz; Carvalhães, Cecilia Helena Vieira Franco Godoy; Ferrarini, Maria Aparecida Gadiani
Abstract Objective: To report a case septic arthritis with a rare pathogen in a immunosuppressed child. Case description: Male patient, 6 years old, had liver transplant five and half years ago due to biliary atresia. Patient was using tacrolimus 1mg q.12h. This patient started to have pain in left foot and ankle and had one episode of fever 3 days before hospital admission. Physical examination showed weight 17kg, height 109cm, temperature 36.4°C, with pain, swelling and heat in the left ankle, without other clinical signs. Initial tests: hemoglobin 11.7g/dL hematocrit 36.4%, leukocyte count 17,600µL-1 (7% banded neutrophils, 70% segmented neutrophils, 2% eosinophils, basophils 1%, 13% lymphocytes, 7% monocytes) C-reactive protein 170.88mg/L. Joint ultrasound showed moderate effusion in the site. Patient was submitted to surgical procedure and Sphingobacterium multivorum was isolated from the effusion. The germ was susceptible to broad spectrum cephalosporins (ceftriaxone and cefepime) and fluoroquinolones (ciprofloxacin and levofloxacin), and it was resistant to carbapenemic antibiotics and aminoglycosides. He was treated intravenously with oxacillin for 15 days and ceftriaxone for 13 days, and orally with ciprofloxacin for 15 days, with good outcome. Comments: The S. multivorum is a gram negative bacillus that belongs to Flavobacteriaceae family and it is considered non-pathogenic. It has rarely been described as a cause of infections in humans, especially in hospital environment and in immunosuppressed patients. This case report is relevant for its unusual etiology and for the site affected, which may be the first case of septic arthritis described. PMID:26915918
van Tuyl, Lilian H D; Plass, Anne Marie C; Lems, Willem F; Voskuyl, Alexandre E; Dijkmans, Ben A C; Boers, Maarten
The Combinatietherapie Bij Reumatoide Artritis (COBRA) trial has proved that combination therapy with prednisolone, methotrexate and sulphasalazine is superior to sulphasalazine monotherapy in suppressing disease activity and radiological progression of early rheumatoid arthritis (RA). In addition, 5 years of follow-up proved that COBRA therapy results in sustained reduction of the rate of radiological progression. Despite this evidence, Dutch rheumatologists seem reluctant to prescribe COBRA therapy. To explore the reasons for the reluctance in Dutch rheumatologists to prescribe COBRA therapy. A short structured questionnaire based on social-psychological theories of behaviour was sent to all Dutch rheumatologists (n = 230). The response rate was 50%. COBRA therapy was perceived as both effective and safe, but complex to administer. Furthermore, rheumatologists expressed their concern about the large number of pills that had to be taken, the side effects of high-dose prednisolone and the low dose of methotrexate. Although the average attitude towards the COBRA therapy was slightly positive (above the neutral point), the majority of responding rheumatologists had a negative intention (below the neutral point) to prescribe COBRA therapy in the near future. The reluctance of Dutch rheumatologists to prescribe effective COBRA therapy may be due to perceptions of complexity of the treatment schedule and negative patient-related consequences of the therapy.
Siloşi, Isabela; Boldeanu, Mihail Virgil; Cojocaru, Manole; Badea, Ramona Georgiana
Aims. In the present study, we aimed to assess the concentrations of IL-13 and IL-17 in serum of patients with early rheumatoid arthritis (eRA), the investigation of correlation between the concentrations of these cytokines and disease activity score, and the concentration of some autoantibodies and the evaluation of the utility of IL-13 and -17 concentration measurements as markers of disease activity. Materials and Methods. Serum samples were collected from 30 patients and from 28 controls and analysed parameters. Results. The serum concentrations of IL-13, IL-17, anti-CCP, and IgM-RF were statistically significantly higher in patients with eRA, compared to the controls. IL-13 concentrations in the severe and moderate groups with eRA were statistically higher than in the mild and control groups. Also, in the case of IL-17, serum concentrations increased proportionally with the disease activity of eRA. We observe that concentrations of IL-13 and -17 did not correlate with autoantibodies. IL-17 concentration significantly positively correlated with CRP, while IL-13 concentration significantly negatively correlated with CRP. Disease activity score, DAS28, was strongly positively correlated with levels of ESR and weakly positively correlated with concentrations of anti-RA33 autoantibodies. IL-13 has a higher diagnostic utility than IL-17, CRP, ESR, IgM-RF, and anti-CCP as markers of disease activity. Conclusions. The presence of higher IL-13 and IL-17 serum levels in patients, compared with those of controls, confirms that these markers, found with high specificity, might be involved in the pathogenesis of eRA. IL-13 and IL-17 might be of better usefulness in the prediction of eRA activity status than IgM-RF and anti-CCP. PMID:27579330
Zhi, Liqiang; Yao, Shuxin; Ma, Wenlong; Zhang, Weijie; Chen, Honggan; Li, Meng; Ma, Jianbing
Rheumatoid arthritis (RA) is a common, chronic autoimmune disease affecting 0.5–1.0% of adults worldwide, including approximately 4.5–5.0 million patients in China. The genetic etiology and pathogenesis of RA have not yet been fully elucidated. Recently, one new RA susceptibility gene (RAD51B) has been identified in Korean and European populations. In this study, we designed a two-stage case-control study to further assess the relationship of common variants in the RAD51B gene with increased risk of RA in a total of 965 RA patients and 2,511 unrelated healthy controls of Han Chinese ancestry. We successfully identified a common variant, rs911263, as being significantly associated with the disease status of RA (P = 4.8 × 10−5, OR = 0.64). In addition, this SNP was shown to be related to erosion, a clinical assessment of disease severity in RA (P = 2.89 × 10−5, OR = 0.52). These findings shed light on the role of RAD51B in the onset and severity of RA. More research in the future is needed to clarify the underlying functional link between rs911263 and the disease. PMID:28361912
Liu, Jung-Tai; Yeh, Horng-Ming; Liu, Shyun-Yeu; Chen, Kow-Tong
Our understanding of psoriatic arthritis has evolved as new knowledge of the disease has emerged. However, the exact prevalence of psoriatic arthritis is unknown, and its pathogenesis has not been fully elucidated. Genetic, environmental, and immunologic factors have all been implicated in disease development. Early diagnosis and treatment have become primary objectives in clinical rheumatology. Psoriatic arthritis not only causes functional impairment, but also increases mortality risk of patients. The advent of new therapeutic agents capable of arresting the progression of joint damage is expected. However, early psoriatic arthritis assessment remains limited. The objectives of this article are to outline the epidemiology, diagnosis, and treatment of psoriatic arthritis and to suggest a paradigm for identifying early psoriatic arthritis patients. PMID:25232529
Support system for patients with rheumatoid arthritis (RA) is a wide variety, such as the health care, the medical economy, the environment, and mental activity. Among these measures, the laws called the social security system are defined. These systems consist of social insurance (medical insurance, long-term care insurance, pension insurance), social welfare (welfare for the disabled) and public health (measures for intractable diseases). As social support under total management of RA, patients can receive mitigation measures and subsidies (physically disabled person's certificate, high-cost medical care, etc.) for high medical expenses at use of biological products, hospitalization and surgery. Furthermore long-term care insurance and disability pension can be used as a further support of home care.
Al-Ani, Mohammad; Weber, Michelle; Winchester, David; Kosboth, Matthew
A 65-year-old man presented with long-standing rheumatoid arthritis (RA), severe fatigue and mild arthritis of metacarpophalaneal joints. Physical examination revealed S3, II/IV decrescendo diastolic murmur and 2+ LL oedema. Anticyclic citrullinated peptide antibodies were >250 units. Echocardiogram showed an 8 cm pericardial mass with no atrial or ventricular collapse and mild to moderate aortic regurgitation. Cardiac MRI defined the mass as a heterogeneous entity attached to the right, anterior and inferior heart borders, with compression on right cardiac structures and the left ventricle. CT-guided biopsy demonstrated fibrinous material without granulomas or infection. Fatigue did not improve on immunosuppression with low-dose prednisone and leflunamide. Cardiac tamponade was confirmed by heart catheterisation and the mass was surgically excised with partial pericardiectomy. The patient had a dramatic improvement and, 4 years later, he remains asymptomatic cardiac wise. This case highlights the clinical significance of pericardial disease in RA and its response to therapy. 2015 BMJ Publishing Group Ltd.
Gómez-Puerta, José A; Cisternas, Ariel; Hernández, M Victoria; Ruiz-Esquide, Virginia; Vilaseca, Isabel; Sanmartí, Raimon
To evaluate the larynx involvement in patients with rheumatoid arthritis (RA) in a clinical setting and correlate with the different clinical features related to more aggressive disease. Cross-sectional study including 36 consecutive patients with RA. Reflux symptoms were evaluated by the Reflux Symptom Index (RSI) and vocal cord impairment by the Voice Handicap Index-10 (VHI-10). Laryngeal involvement was done by videolaryngostroboscopy (VLS). The mean age was 56,3 ± 14 years with a mean disease duration of 2,6 ± 3,1 years (range 0-16 years). Voice use was considered as professional users in 33%. Twenty-four (67%) out of 36 patients had abnormal findings of VLS. One patient had larynx nodules (bamboo nodules). Eleven patients (31%) were diagnosed with muscle tension dysphonia, and there were symptoms and signs of pharyngeal-laryngeal reflux in 23 (64%) patients. No signs of cricoarytenoid joint impairment was found. Organic larynx involvement was uncommon in patients with RA. However symptoms and signs of pharyngeal-laryngeal reflux were seen in around 60% of patients. There was no correlation between the clinical phenotype, severity of disease, immunological profile or treatment with VLS findings. Copyright © 2013 Elsevier España, S.L. All rights reserved.
Ten Klooster, Peter M; Christenhusz, Lieke C A; Taal, Erik; Eggelmeijer, Frank; van Woerkom, Jan-Maarten; Rasker, Johannes J
This study aims to determine whether patients with rheumatoid arthritis (RA) experience more general feelings of guilt and shame than their peers without RA and to examine possible correlates of guilt and shame in RA. In a cross-sectional survey study, 85 out-patients with RA (77 % female; median disease duration, 11 years) and 59 peer controls completed the Experience of Shame Scale (ESS) and the Test of Self-Conscious Affect (TOSCA). Patients additionally completed measures of health status, self-efficacy, cognitive emotion regulation, and numerical rating scales for life satisfaction and happiness. Patients and peer controls were well matched for sociodemographic characteristics. No significant differences between patients and controls were found for guilt or different types of shame as measured with the TOSCA or ESS. In multivariate analyses, female patients reported more feelings of bodily shame and higher guilt proneness, while younger patients reported more character and bodily shame. Worse social functioning and more self-blaming coping strategies were the strongest independent correlates of shame. Shame proneness was only independently associated with more self-blame, whereas guilt proneness was only associated with female sex. None of the physical aspects of the disease, including pain and physical functioning, correlated with feelings of guilt and shame. Patients with longstanding RA do not experience more general feelings of shame or guilt than their peers without RA. Shame and guilt in RA is primarily associated with demographic and psychosocial characteristics and not with physical severity of the disease.
Background Patients with rheumatic diseases including rheumatoid arthritis (RA) are at increased risk for infections related to both the disease and its treatments. These include uncommonly reported infections due to histoplasmosis. Methods Medical record review of all patients with a diagnosis of RA who developed new histoplasmosis infection in an endemic region between Jan 1, 1998 and Jan 30, 2009 and who were seen at Mayo Clinic in Rochester, Minnesota was performed. Results Histoplasmosis was diagnosed in 26 patients. Most patients were on combination therapies; 15 were on anti-tumor necrosis factor (anti-TNF) agents, 15 on corticosteroids and 16 on methotrexate. Most received more than 6 months of itraconazole and/or amphotericin treatment. Two patients died of causes unrelated to histoplasmosis. Anti-TNF treatment was restarted in 4/15 patients, with recurrence of histoplasmosis in one. Conclusions In this largest single center series of patients with RA and histoplasmosis in the era of immunomodulatory therapy, we found that most patients had longstanding disease and were on multiple immunomodulatory agents. Most cases were pulmonary; typical signs and symptoms of disease were frequently lacking. PMID:21605439
Martire, María Victoria; Marino Claverie, Lucila; Duarte, Vanesa; Secco, Anastasia; Mammani, Marta
To find out the factors that are associated with sustained remission measured by DAS28 and boolean ACR EULAR 2011 criteria at the time of diagnosis of rheumatoid arthritis. Medical records of patients with rheumatoid arthritis in sustained remission according to DAS28 were reviewed. They were compared with patients who did not achieved values of DAS28<2.6 in any visit during the first 3 years after diagnosis. We also evaluated if patients achieved the boolean ACR/EULAR criteria. Variables analyzed: sex, age, smoking, comorbidities, rheumatoid factor, anti-CCP, ESR, CRP, erosions, HAQ, DAS28, extra-articular manifestations, time to initiation of treatment, involvement of large joints, number of tender joints, number of swollen joints, pharmacological treatment. Forty five patients that achieved sustained remission were compared with 44 controls. The variables present at diagnosis that significantly were associated with remission by DAS28 were: lower values of DAS28, HAQ, ESR, NTJ, NSJ, negative CRP, absence of erosions, male sex and absence of involvement of large joints. Only 24.71% achieved the boolean criteria. The variables associated with sustained remission by these criteria were: lower values of DAS28, HAQ, ESR, number of tender joints and number of swollen joints, negative CRP and absence of erosions. The factors associated with sustained remission were the lower baseline disease activity, the low degree of functional disability and lower joint involvement. We consider it important to recognize these factors to optimize treatment. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.
Khantisopon, Nuttapong; Louthrenoo, Worawit; Kasitanon, Nuntana; Sivasomboon, Chate; Wangkaew, Suparaporn; Sang-In, Supatra; Jotikasthira, Nitaya; Bandhaya, Panwadee
To evaluate the prevalence and severity of periodontal disease in patients with rheumatoid arthritis (RA) who attended a rheumatology clinic in a university hospital. All consecutive patients with RA who attended the rheumatology clinic between June 2009 and January 2010 were asked to enroll in this study. All participants answered questionnaires, which included demographic data, medical history, medications used and smoking habits. A full mouth periodontal examination, including gingival index, plaque index, probing pocket depth and clinical attachment level was performed. Only cases that had at least 20 teeth were included in this study. Rheumatoid arthritis parameters, including number of tender and swollen joints, erythrocyte sedimentation rate, the presence of rheumatoid factor (RF), hand radiographs, Disease Activity Index (DAS) and health status using the Thai Health Assessment Questionnaire (HAQ), were determined. The association between RA parameters and periodontal condition was examined. There were 196 participants (87.2% female) with a mean age of 51.7 ± 9.70 years, mean disease duration of 9.62 ± 7.0 years and mean DAS score of 4.64 ± 1.25. Eighty-two per cent were RF-positive. Moderate and severe periodontitis were found in 42% and 57%, respectively. Higher age, male gender, previous or current smoking and high level of plaque score were associated with severe periodontal disease. No differences in RA parameters were found between groups of patients who had moderate and severe periodontitis. We found a high prevalence of periodontitis in Thai patients with RA. However, there was no association between RA parameters and periodontal conditions. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.
Ward, Dermot J.
Evidence in support of claims for the existence of a special relationship between personality and rheumatoid arthritis is conflicting. In this study four groups—one of patients with early rheumatoid arthritis, one of patients with chronic rheumatoid arthritis, one of neurotic patients, and a normal control group—were compared by means of the Maudsley Personality Inventory (M.P.I.) and a neurotic trait in childhood (N.T.C.) score. Both arthritis groups had a lower M.P.I. neuroticism score than the normal control group, with greater significance in the chronic arthritis group. The neurotic group had a significantly higher neuroticism score than the other three groups. Both arthritis groups had a lower extraversion score than normal controls, again with greater significance in the chronic arthritis group. The neurotic group scored significantly less than normal controls on the extraversion scale and intermediately between the early and chronic arthritis groups. There was no significant difference between the arthritis groups and the normal control group in the N.T.C. score, but it was significantly increased in the neurotic group. These findings suggest that people with rheumatoid arthritis differ significantly in personality from normal and from neurotic people, that the differences are accentuated with chronicity in the rheumatoid process, and that the differences develop as a result of the arthritis. PMID:4102507
Di Gregorio, F; Priolo, F; Cerase, A; Belli, P; Galossi, A; Magarò, M; Marano, P
irregularities of the cortical bone of the odontoid process. 52% (13/25) of cervical rheumatoid arthritis patients were identified with plain radiographs, 68% (17/25) with CT and 100% (25/25) with MRI. Our preliminary data show that a specific tool for the diagnosis is recommended even in the early disease phases since rheumatoid arthritis commonly affects the craniocervical junction. Studying the craniocervical region is clinically difficult, and diagnostic imaging assessment is essential. Conventional radiography allowed to detect more than half the patients with cervical rheumatoid arthritis, but only in advanced disease stages. On the contrary, MRI had the unique potential of direct and detailed synovial visualization, thus permitting the diagnosis of cervical involvement even in the early phases of the inflammatory process, when CT findings were still negative or questionable.
Sena Corrales, Gabriel; Mora Navas, Laura; Palacios Muñoz, Rosario; García López, Victoria; Márquez Solero, Manuel; Santos González, Jesús
We report a case of gonococcal arthritis in a patient with human immunodeficiency virus (HIV) infection and review 17 previously published cases; only one patient presented urethritis, and blood cultures were positive in one case. Gonococcal arthritis is rare in HIV-infected patients and is not usually associated with other symptoms. It should be considered in the differential diagnosis of acute arthritis in patients with HIV infection. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.
Lequerré, Thierry; Bansard, Carine; Vittecoq, Olivier; Derambure, Céline; Hiron, Martine; Daveau, Maryvonne; Tron, François; Ayral, Xavier; Biga, Norman; Auquit-Auckbur, Isabelle; Chiocchia, Gilles; Le Loët, Xavier; Salier, Jean-Philippe
Introduction Rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms are still poorly understood. Because previous microarray studies have only focused on long-standing (LS) RA compared to osteoarthritis, we aimed to compare the molecular profiles of early and LS RA versus control synovia. Methods Synovial biopsies were obtained by arthroscopy from 15 patients (4 early untreated RA, 4 treated LS RA and 7 controls, who had traumatic or mechanical lesions). Extracted mRNAs were used for large-scale gene-expression profiling. The different gene-expression combinations identified by comparison of profiles of early, LS RA and healthy synovia were linked to the biological processes involved in each situation. Results Three combinations of 719, 116 and 52 transcripts discriminated, respectively, early from LS RA, and early or LS RA from healthy synovia. We identified several gene clusters and distinct molecular signatures specifically expressed during early or LS RA, thereby suggesting the involvement of different pathophysiological mechanisms during the course of RA. Conclusions Early and LS RA have distinct molecular signatures with different biological processes participating at different times during the course of the disease. These results suggest that better knowledge of the main biological processes involved at a given RA stage might help to choose the most appropriate treatment. PMID:19563633
Chikungunya Arthritis Mechanisms in the Americas (CAMA): A cross sectional analysis of chikungunya arthritis patients 22 months post infection demonstrates a lack of viral persistence in synovial fluid
rheumatoid arthritis are being tested in this patient population. However, such therapeutics could be 76 dangerous if active virus is still present...validated rheumatoid 164 arthritis (RA) assessment tool that is a composite score of the number of tender joints, swollen joints, global 165 disease...comorbidities, n (%) 0 1 (13%) 0 0.19 Comorbidity n(%) Rheumatoid arthritis Osteoarthritis Ischemic heart disease Chronic kidney disease
Yu, YiDing; Haynes, Kevin; Love, Thorvardur Jon; Maliha, Samantha; Jiang, Yihui; Troxel, Andrea B.; Hennessy, Sean; Kimmel, Stephen E.; Margolis, David J.; Choi, Hyon; Mehta, Nehal N.; Gelfand, Joel M.
Objectives We aimed to quantify the risk of major adverse cardiovascular events (MACE) among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), and psoriasis without known PsA compared to the general population after adjusting for traditional cardiovascular risk factors. Methods A population-based longitudinal cohort study from 1994–2010 was performed in The Health Improvement Network (THIN), a primary care medical record database in the United Kingdom. Patients aged 18–89 with PsA, RA, or psoriasis were included. Up to 10 unexposed controls matched on practice and index date were selected for each patient with PsA. Outcomes included cardiovascular death, myocardial infarction, cerebrovascular accidents, and the composite outcome (MACE). Cox proportional hazards models were used to calculate the hazard ratios (HR) for each outcome adjusted for traditional risk factors. A priori we hypothesized an interaction between disease status and disease modifying anti-rheumatic drug (DMARD) use. Results Patients with PsA (N=8,706), RA (N=41,752), psoriasis (N=138,424) and unexposed controls (N=81,573) were identified. After adjustment for traditional risk factors, the risk of MACE was higher in PsA patients not prescribed a DMARD (HR 1.24, 95%CI: 1.03 to 1.49), patients with RA (No DMARD: HR 1.39, 95%CI: 1.28 to 1.50, DMARD: HR 1.58, 95%CI: 1.46 to 1.70), patients with psoriasis not prescribed a DMARD (HR 1.08, 95%CI: 1.02 to 1.15) and patients with severe psoriasis (DMARD users: HR 1.42, 95%CI: 1.17 to 1.73). Conclusions Cardiovascular risk should be addressed with all patients affected by psoriasis, psoriatic arthritis or rheumatoid arthritis. PMID:25351522
Essigman, W K
Skin rashes, proteinuria, systemic lupus erythematosus, polymyositis and myasthenia gravis have all been recorded as complications of penicillamine therapy in patients with rheumatoid arthritis. A patient who had developed all 5 is now described. The skin lesion resembled elastosis perforans serpiginosa, which has been reported as a rare side effect in patients with Wilson's disease but not in patients with rheumatoid arthritis treated with penicillamine. Images PMID:6216862
Krishnaswami, Sriram; Hutmacher, Matt M; Robbins, Jeffery L; Bello, Akintunde; West, Christine; Bloom, Bradley J
The objective was to derive dosing recommendations for the use of celecoxib in patients with juvenile rheumatoid arthritis (JRA) using pharmacokinetic (PK) and exposure-response data. PK and efficacy data from a randomized, double-blind, 12-week study of celecoxib dosed at 3 and 6 mg/kg twice a day (bid) as an investigational suspension formulation in 152 JRA patients aged 2 to 17 years, PK data from 36 adult RA patients, and relative bioavailability data in healthy adults comparing suspension or capsule sprinkles with the commercial capsule were analyzed. Typical oral clearance (L/h) values were 40% and 24% lower in patients weighing 10 and 25 kg, respectively, compared with a 70-kg patient. Longitudinal, logistic pharmacodynamic models incorporating linear effects of dose/area under the plasma concentration-time curve (AUC) over 0 to 12 hours (AUC(0-12)) suggested that the percentage of responders increased with celecoxib exposure. Systemic exposures (AUC) were similar for the suspension, capsule sprinkles, and intact capsule. Administration of a 50-mg bid capsule (or sprinkles) for patients weighing 10 to 25 kg and 100 mg bid for patients >25 kg was predicted to yield similar exposures and response rates as those observed in the JRA trial. Doses and dosage forms not studied in the JRA trial were approved based on the results of this analysis.
Konijn, Nicole P C; van Tuyl, Lilian H D; Boers, Maarten; den Uyl, Debby; Ter Wee, Marieke M; Kerstens, Pit; Voskuyl, Alexandre E; Nurmohamed, Michael; van Schaardenburg, Dirkjan; Lems, Willem F
To investigate the longitudinal relationship between disease activity and self-reported physical activity (PA) in patients with early rheumatoid arthritis during the first year of treatment with combination therapy. PA was measured with the Short Questionnaire to Assess Health-Enhancing Physical Activity at baseline, 13 weeks, 26 weeks, and 52 weeks after start of treatment in the context of the Combinatietherapie Bij Reumatoïde Artritis-Light trial. The reported PA classified patients as meeting or not meeting the World Health Organization (WHO) PA guideline (cutoff: 150 minutes of moderate-to-intense activity per week). Other measurements included the Disease Activity Score (DAS). Since both treatment arms showed equal treatment effect, these were analyzed as 1 group with simple before-after analyses and generalized estimating equations (GEE). In these analyses, 140 patients (86% of the trial population, 66% women, mean age 52 years) with complete data were included. At entry, 69% of the patients met the WHO PA guideline, increasing to 90% at week 13, and remaining stable at 89% after 1 year (P < 0.001). Mean DAS improved from 4.0 to 1.8 during the first year of treatment (P < 0.001). In GEE analyses, DAS decreases were significantly associated with PA increases (P = 0.008). Patients with clinically relevant responses (expressed as DAS remission, European League Against Rheumatism good response or American College of Rheumatology criteria for 70% improvement response) showed higher PA levels compared to nonresponders, regardless of the definition of response, for both the WHO and Dutch PA guideline. Early rheumatoid arthritis patients using combination therapy improved both disease activity and PA, a beneficial effect persisting for at least 1 year. © 2016, American College of Rheumatology.
Machado, Marina Amaral de Ávila; Moura, Cristiano Soares de; Ferré, Felipe; Bernatsky, Sasha; Rahme, Elham; Acurcio, Francisco de Assis
To evaluate treatment persistence in patients with rheumatoid arthritis and ankylosing spondylitis who started therapies with disease-modifying antirheumatic drugs (DMARD) and tumor necrosis factor blockers (anti-TNF drugs). This retrospective cohort study from July 2008 to September 2013 evaluated therapy persistence, which is defined as the period between the start of treatment until it is discontinued, allowing for an interval of up to 30 days between the prescription end and the start of the next prescription. Odds ratio (OR) with 95% confidence intervals (95%CI) were calculated by logistic regression models to estimate the patients' chances of persisting in their therapies after the first and after the two first years of follow-up. The study included 11,642 patients with rheumatoid arthritis - 2,241 of these started on anti-TNF drugs (+/-DMARD) and 9,401 patients started on DMARD - and 1,251 patients with ankylosing spondylitis - 976 of them were started on anti-TNF drugs (+/-DMARD) and 275 were started on DMARD. In the first year of follow-up, 63.5% of the patients persisted in their therapies with anti-TNF drugs (+/-DMARD) and 54.1% remained using DMARD in the group with rheumatoid arthritis. In regards to ankylosing spondylitis, 79.0% of the subjects in anti-TNF (+/-DMARD) group and 41.1% of the subjects in the DMARD group persisted with their treatments. The OR (95%CI) for therapy persistence was 1.50 (1.34-1.67) for the anti-TNF (+/-DMARD) group as compared with the DMARD group in the first year for the patients with rheumatoid arthritis, and 2.33 (1.74-3.11) for the patients with ankylosing spondylitis. A similar trend was observed at the end of the second year. A general trend of higher rates of therapy persistence with anti-TNF drugs (+/-DMARD) was observed as compared to DMARD in the study period. We observed higher persistence rates for anti-TNF drugs (+/-DMARD) in patients with ankylosing spondylitis as compared to rheumatoid arthritis; and a higher
Jalal, Hawre; O'Dell, James R; Bridges, S Louis; Cofield, Stacey; Curtis, Jeffrey R; Mikuls, Ted R; Moreland, Larry W; Michaud, Kaleb
To evaluate the cost-effectiveness of all 4 interventions in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) clinical trial: immediate triple (IT), immediate etanercept (IE), step-up triple (ST), and step-up etanercept (SE). Step-up interventions started with methotrexate and added either etanercept or sulfasalazine plus hydroxychloroquine to patients with persistent disease activity. We built a Markov cohort model that uses individual-level data from the TEAR trial, published literature, and supplemental clinical data. Costs were in US dollars, benefits in quality-adjusted life years (QALYs), perspective was societal, and the time horizon was 5 years. The immediate strategies were more efficacious than step-up strategies. SE and IE were more costly than ST and IT, primarily due to treatment cost differences. In addition, IT was the least expensive and most effective strategy when the time horizon was 1 and 2 years. When the time horizon was 5 years, IE was marginally more effective than IT (3.483 versus 3.476 QALYs), but IE was substantially more expensive than IT ($148,800 versus $52,600), producing an incremental cost-effectiveness ratio of $12.5 million per QALY. These results were robust to both one-way deterministic and joint probabilistic sensitivity analyses. IT was highly cost-effective in the majority of scenarios. Although IE was more effective in 5 years, a substantial reduction in the cost of biologic agents was required in order for IE to become cost-effective in early aggressive RA under willingness-to-pay thresholds that most health care settings may find acceptable. © 2016, American College of Rheumatology.
Dalmády, Szandra; Kiss, Mária; Képíró, László; Kovács, László; Sonkodi, Gábor; Kemény, Lajos; Gyulai, Rolland
Antibodies against citrullinated proteins/peptides (ACPAs), and especially antibodies targeting mutated citrullinated vimentin (anti-MCVs), are novel biomarkers of rheumatoid arthritis (RA). Whereas ACPAs are specific and sensitive markers for RA, there have hardly been any reports relating to ACPAs in psoriatic arthritis (PsA) or in psoriasis without joint symptoms (PsO). The aim of the present study was to investigate the prevalence of anti-MCVs in PsA and PsO. Serum anti-MCV titers were measured in 46 PsA and 42 PsO patients and in 40 healthy controls by means of a commercial enzyme-linked immunosorbent assay. The potential correlations of the serum autoantibody levels with several clinical and laboratory parameters were examined. The anti-MCV levels in the PsA patients were significantly higher than those in the PsO group. Among the clinical variables, the presence of tender knee joints and nail psoriasis was significantly associated with anti-MCV positivity in the PsA patients. Higher anti-MCV titers in the PsO patients were associated with a more severe disease course and with the early onset of psoriatic skin symptoms. Our results suggest that anti-MCVs can be used as novel markers in the diagnosis of PsA and in a subset of PsO patients. PMID:23573111
Goëb, Vincent; Thomas-L'Otellier, Marlène; Daveau, Romain; Charlionet, Roland; Fardellone, Patrice; Le Loët, Xavier; Tron, François; Gilbert, Danièle; Vittecoq, Olivier
Introduction The aim of our study was to identify new early rheumatoid arthritis (RA) autoantibodies. Methods Sera obtained from 110 early untreated RA patients (<6 months) were analyzed by western blot using HL-60 cell extract, separated on one-dimensional and two-dimensional gel electrophoresis (1-DE, 2-DE). Sera from 50 healthy blood donors and 20 patients with non-RA rheumatisms were used as controls for 1-DE and 2-DE, respectively. The immunoreactive proteins were identified by MALDI-TOF mass spectrometric analysis and the presence of potential sites of citrullination in each of these proteins was evaluated. FT-ICR mass spectrometry was used to verify experimentally the effect of citrullination upon the mass profile observed by MALDI-TOF analysis. Results The 110 1-DE patterns allowed detection of 10 recurrent immunoreactive bands of 33, 39, 43, 46, 51, 54, 58, 62, 67 and 70 kDa, which were further characterized by 2-DE and proteomic analysis. Six proteins were already described RA antigens: heterogeneous nuclear ribonucleoprotein A2/B1, aldolase, α-enolase, calreticulin, 60 kDa heat shock protein (HSP60) and BiP. Phosphoglycerate kinase 1 (PGK1), stress-induced phosphoprotein 1 and the far upstream element-binding proteins (FUSE-BP) 1 and 2 were identified as new antigens. Post-translational protein modifications were analyzed and potentially deiminated peptides were found on aldolase, α-enolase, PGK1, calreticulin, HSP60 and the FUSE-BPs. We compared the reactivity of RA sera with citrullinated and noncitrullinated α-enolase and FUSE-BP linear peptides, and showed that antigenicity of the FUSE-BP peptide was highly dependent on citrullination. Interestingly, the anti-cyclic citrullinated peptide antibody (anti-CCP2) status in RA serum at inclusion was not correlated to the reactivity directed against FUSE-BP citrullinated peptide. Conclusions Two categories of antigens, enzymes of the glycolytic family and molecular chaperones are also targeted by the
Nimmrich, S; Horneff, G
The risk of herpes zoster among patients with juvenile idiopathic arthritis (JIA) exposed to biologics has not been evaluated. We determined incidence rates of herpes zoster among children with JIA in correlation with medication at time of occurrence and total drug exposure. The German biologics register database was used to identify patients with herpes zoster. Crude infection rates and incidence ratios (IRR) were compared to published rates. Demographics and overall exposure and particular exposure time to corticosteroids, immunosuppressive drugs and biologics were analyzed. The JIA cohort included 3,042 patients with 5,557.9 person-years of follow-up; 1,628 have used corticosteroids, 2,930 methotrexate and 1,685 etanercept. In total, 17 herpes zoster events have been documented [6/1,000 patients (3.5-9.0); 3.1/1,000 patient-years (1.9-4.9)]. Thus, the incidence rate in JIA patients was higher than expected [IRR 2.9 (1.8-4.5), p < 0.001]. In all patients, the event resolved completely. There were two complications, one patient developed intercostal neuralgia, and one had a recurrent herpes zoster. Compared to the healthy population, a significant higher IRR is observed in JIA patients who received a monotherapy with etanercept or in combination with steroids and methotrexate, but not in JIA patients exposed to methotrexate without biologics. In comparison with our control group of patients treated with methotrexate, the IRR was higher for exposure to etanercept monotherapy and combination of etanercept and corticosteroids irrespective of methotrexate use. A generally higher incidence rate in JIA patients treated with etanercept was observed. No serious or refractory manifestations occurred.
Johnson, S; Schentag, C; Gladman, D
Objective: To investigate the prevalence of autoantibodies in biological agent naive patients with psoriatic arthritis (PsA). Methods: 94 consecutive, prospectively collected, biological agent naive patients with PsA at the University of Toronto PsA clinic underwent clinical and laboratory assessment. Disease activity was assessed by the number of actively inflamed joints, and the Psoriasis Activity and Severity Index (PASI) score. Antinuclear antibodies (ANA), rheumatoid factor (RF), double stranded DNA (dsDNA), Ro, La, Smith, and RNP were tested. Descriptive statistics and non-parametric tests were used to analyse the data. Results: 44/94 (47%) patients with PsA were ANA positive (⩾1/40); 13/94 (14%) had a clinically significant titre of ⩾1/80. Three per cent had dsDNA antibodies, 2% had RF and anti-Ro antibodies, 1% had anti-RNP antibodies, and none had anti-La or anti-Smith antibodies. Conclusions: The background prevalence of ANA ⩾1/80 in patients with PsA was 14%, with very few patients having specific lupus antibodies. This should serve as a baseline figure for the frequency of autoantibodies in biological agent naive patients with PsA for studies of the use of anti-TNFα agents. PMID:15834057
Bello, Alfonso E; Perkins, Elizabeth L; Jay, Randy; Efthimiou, Petros
Methotrexate (MTX) remains the cornerstone therapy for patients with rheumatoid arthritis (RA), with well-established safety and efficacy profiles and support in international guidelines. Clinical and radiologic results indicate benefits of MTX monotherapy and combination with other agents, yet patients may not receive optimal dosing, duration, or route of administration to maximize their response to this drug. This review highlights best practices for MTX use in RA patients. First, to improve the response to oral MTX, a high initial dose should be administered followed by rapid titration. Importantly, this approach does not appear to compromise safety or tolerability for patients. Treatment with oral MTX, with appropriate dose titration, then should be continued for at least 6 months (as long as the patient experiences some response to treatment within 3 months) to achieve an accurate assessment of treatment efficacy. If oral MTX treatment fails due to intolerability or inadequate response, the patient may be “rescued” by switching to subcutaneous delivery of MTX. Consideration should also be given to starting with subcutaneous MTX given its favorable bioavailability and pharmacodynamic profile over oral delivery. Either initiation of subcutaneous MTX therapy or switching from oral to subcutaneous administration improves persistence with treatment. Upon transition from oral to subcutaneous delivery, MTX dosage should be maintained, rather than increased, and titration should be performed as needed. Similarly, if another RA treatment is necessary to control the disease, the MTX dosage and route of administration should be maintained, with titration as needed. PMID:28435338
Krause, Megan L; Matteson, Eric L
A multidisciplinary approach is required to care for patients with rheumatoid arthritis (RA) in the perioperative period. In preparation for surgery, patients must have a cardiovascular risk assessment performed due to the high risk of heart disease in patients with RA. Treatment of RA is with immunomodulatory medications, which present unique challenges for the perioperative period. Currently, there is no consensus on how to manage disease modifying antirheumatic drug (DMARD) therapy in the perioperative setting. Much of the data to guide therapy is based on retrospective cohort data. Choices regarding DMARDs require an individualized approach with collaboration between surgeons and rheumatologists. Consensus regarding biologic therapy is to hold the therapy in the perioperative period with the length of time dictated by the half-life of the medication. Special attention is required at the time of surgery for potential need for stress dose steroids. Further, there must be close communication with anesthesiologists in terms of airway management particularly in light of the risk for cervical spine disease. There are no consensus guidelines regarding the requirement for cervical spine radiographs prior to surgery. However, history and exam alone cannot be relied upon to identify cervical spine disease. Patients with RA who undergo joint replacement arthroplasty are at higher risk for infection and dislocation compared to patients with osteoarthritis, necessitating particular vigilance in postoperative follow up. This review summarizes available evidence regarding perioperative management of patients with RA.
Lempp, Heidi; Hofmann, Darija; Hatch, Stephani L; Scott, David L
Combinations of disease-modifying anti-rheumatic drugs (DMARDs) are increasingly used to control active rheumatoid arthritis (RA); however there is little information about patients' perspectives, their expectations, concerns and experiences of this intensive treatment. We interviewed a quota sample of 18 patients from a single tertiary outpatient clinic, stratified by gender, ethnicity and age, based on the outpatient clinic population. Patients with early RA (<2 years) received combined conventional DMARDs; patients with established RA (>2 years) received combined conventional DMARDs or DMARDs with biologics. Four main themes emerged from the analytical framework: (i) patients' expectations about the combined treatment focuses mainly on physical symptoms; (ii) the impact of the treatment on quality of life varied with the new medication in both groups (iii) concerns about new interventions concentrated mainly on potential side effects; and (iv) combination therapy can be self-managed in close collaboration with clinic staff, but this requires individualised management approaches. These themes resonate with von Korff's collaborative management of chronic illness model. To our knowledge this is the first qualitative study that examined systematically in patients with early and established RA their expectations, impact on quality of life, concerns about side effects and the management of the treatment when taking combined medication with DMARDs or DMARDs and biologics. Patients have generally positive views of combination DMARDs. Within routine practice settings, achieving medication concordance with complex combined DMARD regimens is challenging, and the concerns vary between patients; careful individual assessments are essential to successfully deliver such intensive treatment.
Palmblad, Karin; Erlandsson-Harris, Helena; Tracey, Kevin J.; Andersson, Ulf
This study was performed to elucidate pathophysiological events before and during the course of collagen-induced arthritis in Dark Agouti rats, a model for rheumatoid arthritis. Kinetic studies of local cytokine responses were determined using immunohistochemical techniques, quantified by computer-assisted image analysis. We recently reported that the macrophage-pacifying agent CNI-1493 successfully ameliorated collagen-induced arthritis. In the present trial, we investigated the potential of CNI-1493 to down-regulate pro-inflammatory cytokines. Synovial cryosections were analyzed at various time points for the presence of interleukin (IL)-1β, tumor necrosis factor (TNF), and transforming growth factor (TGF)-β. Unexpectedly, an early simultaneous TNF and IL-1β expression was detected in resident cells in the lining layer, preceding disease onset and inflammatory cell infiltration by >1 week. The predominant cytokine synthesis by synovial (ED1+) macrophages coincided with clinical disease. TNF production greatly exceeded that of IL-1β. CNI-1493 treatment did not affect the early disease-preceding TNF and IL-1β synthesis in the lining layer. However, after disease onset, CNI-1493 intervention resulted in a pronounced reduced IL-1β and in particular TNF expression. Furthermore, CNI-1493 significantly up-regulated synthesis of the anti-inflammatory cytokine TGF-β and thereby shifted the balance of pro-inflammatory and anti-inflammatory cytokines in the arthritic joint in a beneficial way. PMID:11159186
Navarro-Millán, Iris; Charles-Schoeman, Christina; Yang, Shuo; Bathon, Joan M.; Bridges, S. Louis; Chen, Lang; Cofield, Stacey S.; Dell’Italia, Louis J.; Moreland, Larry W.; O’Dell, James R.; Paulus, Harold E.; Curtis, Jeffrey R.
Objective To study changes in lipid profiles at 24 weeks among early rheumatoid arthritis (RA) patients participating in the Treatment of Early Rheumatoid Arthritis (TEAR) Trial randomized to initiate methotrexate plus etanercept (MTX+ETA), triple therapy (TT) [MTX plus sulfasalazine plus hydroxychloroquine] or aggressively-titrated MTX monotherapy. Methods The TEAR biorepository study had 459 participating patients. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured in serum plasma at 0 and 24 weeks. Results At 24 weeks, there were statistically significant mean increases in cholesterol levels in the MTX + ETA, TT, and MTX monotherapy arms, the observed increases were 31.4, 28.7 and 30 mg/dL in LDL-C; 19.3, 22.3 and 20.6 mg/dL in HDL-C and 56.8, 53 and 57.3 mg/dL values in TC (p < 0.001 all compared to baseline). There was a statistically significant decrease in TC/HDL-C ratio at 24 weeks in all 3 treatment groups from baseline. There was no difference in any lipid changes between the 3 treatment arms. After multivariable adjustment, change in C-reactive protein was associated with change in LDL-C (p=0.03), HDL-C (p=0.09), and TC (p=0.01), but disease activity score in 28-joints was not. Baseline glucocorticoid use was associated with changes in HDL-C (p=0.03) and TC (p=0.02). Conclusion Levels of TC, LDL-C, and HDL-C increased equivalently shortly after initiation of MTX + ETA, TT and MTX monotherapy among early RA patients with active disease participating in a clinical trial. The clinical relevance of short term changes in traditional lipids on cardiovascular outcomes remains to be determined. PMID:23460074
Venegas-Pont, Marcia; Davis, John M.; Crowson, Cynthia S; Gabriel, Sherine E.; Matteson, Eric L.
Background Patients with rheumatoid arthritis (RA) undergo radiologic investigations for disease and comorbidity evaluation. The actual use of radiologic imaging in RA is unknown. Methods Using the Rochester Epidemiology Project medical record linkage system, adult patients from previously assembled population-based cohorts of Olmsted County, Minnesota residents who fulfilled 1987 ACR criteria for RA in 1988-2007, and comparator subjects without RA of similar age and sex were studied. Data on all radiologic procedures performed were collected. Results The study included 650 patients with RA and 650 patients without RA. Patients with RA had significantly more radiographs of the chest (RR: 1.33, 95% CI: 1.28-1.38), upper extremity (RR: 2.97, 95% CI: 2.80-3.17), lower extremity (RR: 2.05, 95% CI: 1.94-2.16), spine (RR: 1.46, 95% CI: 1.35-1.59), and hip, pelvis or sacroiliac joints (RR: 1.14, 95% CI: 1.03-1.26), as well as bone radionuclide (RR: 1.90, 95% CI: 1.50-2.44) and DXA imaging (RR: 1.77, 95% CI: 1.59-1.98) compared to patients without RA. Among patients with RA, having RF+ was associated with an increased likelihood of undergoing radiologic procedures (RR: 1.05, 95% CI: 1.02, 1.07). Women with RA underwent more imaging procedures than men (RR: 1.20 95% CI: 1.16-1.23). Conclusions Patients with RA undergo more radiologic procedures than patients without RA. Among patients with RA, women and patients with positive RF have more radiologic procedures. The utilization of radiography is likely a reflection of overall disease burden; the role of various imaging modalities is in flux and will likely change in ensuing years. PMID:25539428
Goeppinger, J; Lorig, K
Systematic development and testing of the efficacy of educational interventions to improve functioning, prevent disability, and reduce the impact of chronic disease has been limited, perhaps because many chronic diseases disable, do not kill, and because they are managed largely within home, work, and community environments and not within the medical care system. Until recently, these factors contributed to a paucity of arthritis educational interventions. But since the impetus provided by the establishment of the Multipurpose Arthritis Centers Program of the NIH (1977), a number of arthritis patient education programs have been established and evaluated. This chapter summarizes findings from community-based arthritis patient education studies conducted between 1980 and 1995, critiques the methods of these studies, and provides guidance for state-of-the-art community-based intervention research aimed at reducing the individual and social impact of arthritis and other chronic diseases.
Community access cable television channels can be used to provide low-cost health programming in many communities. This article describes a study undertaken to ascertain the extent to which arthritis patients could be targeted by arthritis-related programming over a local cable system. A number of publicity sources were used to advertise the programs to a preidentified group and the public at large. Telephone and written surveys revealed that the programming garnered a moderate viewing audience composed preponderantly of arthritis patients. Some conceptual and practical issues involved in targeting chronic patient groups for health programming are discussed.
Thomas, D; Gallus, A S; Brooks, P M; Tampi, R; Geddes, R; Hill, W
The mechanism of D-penicillamine induced thrombocytopenia in rheumatoid arthritis was investigated by measuring platelet life-span and platelet production rate in 2 groups of rheumatoid arthritis patients treated with 250-750 mg/day D-penicillamine, 14 with a normal platelet count and 9 with thrombocytopenia (platelet count 50-130 X 10(9)/1). Age matched control patients not treated with D-penicillamine included 14 with rheumatoid arthritis and 9 with osteoarthritis. The platelet life-span was normal, but platelet production rate was significantly reduced in the thrombocytopenic patients, suggesting that D-penicillamine causes thrombocytopenia through bone marrow suppression. PMID:6742902
De simone, Clara; Caldarola, Giacomo; D'Agostino, Magda; Carbone, Angelo; Guerriero, Cristina; Bonomo, Lorenzo; Amerio, Pierluigi; Magarelli, Nicola
Background. Given that clinical evaluation may underestimate the joint damage and that early treatment can slow down psoriatic arthritis (PsA) progression, screening psoriasis patients with imaging tools that can depict early PsA changes would entail clear benefits. Objective. To compare the ability of X-ray and ultrasound (US) examination in detecting morphological abnormalities consistent with early PsA in patients with psoriasis, using rheumatological evaluation as the gold standard for diagnosis. Methods. Patients with chronic plaque psoriasis and no previous PsA diagnosis attending our outpatient dermatology clinic and reporting finger/toe joint and/or tendon pain underwent X-ray and US evaluation; they were subsequently referred to a rheumatologist for clinical examination and review of imaging findings. Results. Abnormal US and/or X-ray findings involving at least one finger and/or toe (joints and/or tendons) were seen in 36/52 patients: 11 had one or more X-ray abnormalities, including erosion, joint space narrowing, new bone formation, periarticular soft tissue swelling, and periarticular osteoporosis; 36 had suspicious changes on US. Conclusion. US proved valuable in detecting joint and/or tendon abnormalities in the fingers and toes of patients with suspicious changes. The dermatologist should consider US to obtain an accurate assessment of suspicious findings. PMID:21461353
Heydari, Nahid; Hajiabolhassani, Fahimeh; Fatahi, Jamileh; Movaseghi, Shafieh; Jalaie, Shohreh
Background: Rheumatoid arthritis (RA) is an autoimmune systemic disease. Most common autoimmune diseases are multisystem disorders that may also present with otological manifestations, and autoimmune inner ear disease accompanied by vestibular dysfunction. This study aimed to compare the vestibular function between RA patients and normal subjects using cervical vestibular evoked myogenic potentials (cVEMPs). Methods: In this cross- sectional study, 25patients with RA (19 female and 6 male: mean (±SD) age, 40.00 (±7.92) years) and 20 healthy subjects (15 female and 5 male: mean (±SD) age, 35.35 (±10.48) years) underwent cVEMPs, using 500 Hz-tone bursts at 95 dB nHL intensity level. Data were analyzed using independent sample t-test through SPSS software v. 16. Results: The mean peak latency of p13 was significantly higher in RA patients (p<0.001). The mean peak latency of n23 was significantly higher in patients in the left ear (p=0.03). Vestibular evoked myogenic potential (VEMP) responses were present in all (100%) of the participants. There were no significant differences in mean peak to peak amplitude and amplitude ratio between the two groups. Conclusion: According to the prolonged latency of VEMP responses in RA patients, lesions in the retrolabyrinthine, especially in the vestibulospinal tract are suspected. PMID:26478874
Patients with rheumatic diseases, including rheumatoid arthritis and osteoarthritis, almost universally describe pain and stiffness as important contributors to reduced health-related quality of life. Of the treatment options available, NSAIDs are the most widely used agents for symptomatic treatment. NSAIDs are effective anti-inflammatory and analgesic drugs by virtue of their ability to inhibit biosynthesis of prostaglandins at the level of the cyclooxygenase enzyme. However, many of the adverse effects of NSAIDs are also related to inhibition of prostaglandin production, making their use problematic in some patient populations. For the clinician, understanding the biology of prostaglandin as it relates to gastrointestinal, renal, and cardiovascular physiology and the pharmacologic properties of specific NSAIDs is key to using these drugs safely. Of particular importance is the recognition of co-morbid conditions and concomitant drugs that may increase the risk of NSAIDs in particular patients. In patients with risk factors for NSAID toxicity, using the lowest dose of a drug with a short half-life only when it is needed is likely to be the safest treatment option. For those patients whose symptoms cannot be managed with intermittent treatment, using protective strategies is essential. PMID:24267197
Siloşi, Isabela; Boldeanu, Lidia; Biciuşcă, Viorel; Bogdan, Maria; Avramescu, Carmen; Taisescu, Citto; Padureanu, Vlad; Boldeanu, Mihail Virgil; Dricu, Anica; Siloşi, Cristian Adrian
In the present study, we aimed to estimate the concentrations of cytokines (interleukin 6, IL-6, tumor necrosis factor-α, TNF-α) and auto-antibodies (rheumatoid factor IgM isotype, IgM-RF, antinuclear auto-antibodies, ANA, anti–cyclic citrullinated peptide antibodies IgG isotype, IgG anti-CCP3.1, anti-cardiolipin IgG isotype, IgG anti-aCL) in serum of patients with eRA (early rheumatoid arthritis) and HCVrA (hepatitis C virus-related arthropathy) and to assess the utility of IL-6, TNF-α together with IgG anti-CCP and IgM-RF in distinguishing between patients with true eRA and HCVrA, in the idea of using them as differential immunomarkers. Serum samples were collected from 54 patients (30 diagnosed with eRA-subgroup 1 and 24 with HCVrA-subgroup 2) and from 28 healthy control persons. For the evaluation of serum concentrations of studied cytokines and auto-antibodies, we used immunoenzimatique techniques. The serum concentrations of both proinflammatory cytokines were statistically significantly higher in patients of subgroup 1 and subgroup 2, compared to the control group (p < 0.0001). Our study showed statistically significant differences of the mean concentrations only for ANA and IgG anti-CCP between subgroup 1 and subgroup 2. We also observed that IL-6 and TNF-α better correlated with auto-antibodies in subgroup 1 than in subgroup 2. In both subgroups of patients, ROC curves indicated that IL-6 and TNF-α have a higher diagnostic utility as markers of disease. In conclusion, we can say that, due to high sensitivity for diagnostic accuracy, determination of serum concentrations of IL-6 and TNF-α, possibly in combination with auto-antibodies, could be useful in the diagnosis and distinguishing between patients with true eRA and HCV patients with articular manifestation and may prove useful in the monitoring of the disease course. PMID:28629188
Ziebolz, Dirk; Pabel, Sven O; Lange, Katharina; Krohn-Grimberghe, Berndt; Hornecker, Else; Mausberg, Rainer F
A limited number of studies suggest a prevalence of periodontal pathogens in patients with rheumatoid arthritis (RA); however, results are inconsistent. The aim of this study is to investigate clinical periodontal and microbiologic parameters in patients with RA. Sixty-six patients with RA, aged 49.5 ± 8.4 years, participated in the study. The periodontal classification was assessed with the periodontal screening index (PSR/PSI) allocated to the following parameters: 1) healthy; 2) gingivitis (PSR/PSI score 0 to 2, maximum one sextant score; 3) moderate periodontitis (>1 sextant PSR/PSI score 3, maximum one sextant score; or, 4) severe periodontitis (>1 sextant PSR/PSI score 4). Pool samples were taken for microbiologic (polymerase chain reaction) analysis for the presence of 11 periodontal pathogens. Statistical analysis was by non-parametric analysis of covariance. No patients were periodontally healthy: 24 patients were classified as having gingivitis; 18 patients had moderate periodontitis; 23 patients had severe periodontitis; and one patient was toothless. For most patients, Fusobacterium nucleatum (98%), Eikenella corrodens (91%), and Parvimonas micra (previously Peptostreptococcus micros; 88%) were above the detection threshold. Strong periodontal pathogens were less frequently detected: Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans, 16%); Porphyromonas gingivalis (58%); and Tannerella forsythia (previously T. forsythensis, 78%). Statistical analysis showed no significant influence of rheumatic factor (P = 0.33) on periodontal classification and on microbiologic parameters (P >0.05). Only smoking showed a significant influence (P = 0.0004) on the periodontal classification and in the case of E. corrodens (P = 0.02). Most patients with RA in this study showed moderate-to-severe periodontitis and the presence of periodontal pathogens. No association was found between rheumatic factor on periodontal classification and
Peters, M J L; Symmons, D P M; McCarey, D; Dijkmans, B A C; Nicola, P; Kvien, T K; McInnes, I B; Haentzschel, H; Gonzalez-Gay, M A; Provan, S; Semb, A; Sidiropoulos, P; Kitas, G; Smulders, Y M; Soubrier, M; Szekanecz, Z; Sattar, N; Nurmohamed, M T
To develop evidence-based EULAR recommendations for cardiovascular (CV) risk management in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). A multidisciplinary expert committee was convened as a task force of the EULAR Standing Committee for Clinical Affairs (ESCCA), comprising 18 members including rheumatologists, cardiologists, internists and epidemiologists, representing nine European countries. Problem areas and related keywords for systematic literature research were identified. A systematic literature research was performed using MedLine, Embase and the Cochrane library through to May 2008. Based on this literature review and in accordance with the EULAR's "standardised operating procedures", the multidisciplinary steering committee formulated evidence-based and expert opinion-based recommendations for CV risk screening and management in patients with inflammatory arthritis. Annual CV risk assessment using national guidelines is recommended for all patients with RA and should be considered for all patients with AS and PsA. Any CV risk factors identified should be managed according to local guidelines. If no local guidelines are available, CV risk management should be carried out according to the SCORE function. In addition to appropriate CV risk management, aggressive suppression of the inflammatory process is recommended to further lower the CV risk. Ten recommendations were made for CV risk management in patients with RA, AS and PsA. The strength of the recommendations differed between RA on the one hand, and AS and PsA, on the other, as evidence for an increased CV risk is most compelling for RA.
Introduction The purpose of this study was to investigate the effectiveness of adalimumab in enthesitis and peripheral arthritis in patients with ankylosing spondylitis (AS). Methods Adults with active AS (Bath ankylosing spondylitis disease activity index [BASDAI] ≥ 4) received adalimumab 40 mg every other week with standard antirheumatic therapies in a 12-week, open-label study. Effectiveness in enthesitis was assessed using the Maastricht ankylosing spondylitis enthesitis score (MASES, 0-13) and by examining the plantar fascia in patients with enthesitis (≥ 1 inflamed enthesis) at baseline; effectiveness in peripheral arthritis was evaluated using tender and swollen joint counts (TJC, 0-46; SJC, 0-44) in patients with peripheral arthritis (≥ 1 swollen joint) at baseline. Overall effectiveness measures included Assessment of SpondyloArthritis International Society 20% response (ASAS20). Results Of 1,250 patients enrolled, 686 had enthesitis and 281 had peripheral arthritis. In 667 patients with MASES ≥ 1 at baseline, the median MASES was reduced from 5 at baseline to 1 at week 12. At week 12, inflammation of the plantar fascia ceased in 122 of 173 patients with inflammation at baseline. The median TJC in 281 patients with SJC ≥ 1 at baseline was reduced from 5 at baseline to 1 at week 12; the median SJC improved from 2 to 0. ASAS20 responses were achieved by 70.5% of 457 patients with no enthesitis and no arthritis; 71.0% of 512 patients with only enthesitis; 68.0% of 107 patients with only arthritis; and 66.7% of 174 patients with both. Conclusions Treatment with adalimumab improved enthesitis and peripheral arthritis in patients with active AS. Trial registration ClinicalTrials.gov NCT00478660. PMID:20230622
Rahmani, Maryam; Chegini, Hosein; Najafizadeh, Seyed Reza; Azimi, Mohammad; Habibollahi, Peiman; Shakiba, Madjid
Nowadays, there is a trend toward early diagnosis and treatment of rheumatoid arthritis (RA) especially in patients with early signs of bone erosion which can be detected by magnetic resonance imaging (MRI). The aim of following study is to compare the sensitivity and specificity of ultrasonography (US) and conventional radiography (CR) compared to MRI for early detection of bone erosion in RA patients. In 12 patients with RA diagnosis, 120 first to fifth metacarpophalangeal joints and 96 second to fifth proximal interphalangeal joints were examined. Non-contrast MRI, US and CR were performed for bone erosion evaluation. For further analysis, the patients were divided in two equal groups according to disease activity score (DAS28). The overall sensitivity and specificity of US compared to MRI in detecting bone erosion were 0.63 and 0.98, respectively with a considerable agreement (kappa = 0.68, p < 0.001). Sensitivity and specificity of CR compared to MRI in detecting bone erosion were 0.13 and 1.00, respectively (kappa = 0.20, p < 0.001). In patients with more active disease, the sensitivity and specificity were 0.67 and 0.99 (kappa = 0.74, p < 0.001) compared to 0.59 and 0.97 (kappa = 0.61, p < 0.001) for the rest of patients according to DAS28. Conclusively, these findings reveal an acceptable agreement between US and MRI for detection of bone erosion in patients with early RA but not CR. US might be considered as a valuable tool for early detection of bone erosion especially when MRI is not available or affordable. Besides, it seems the US could be more reliable when the disease is more active.
Huo, Yinghe; De Hair, Maria J H; Shaib, Yasmin O; van der Heijde, Désirée; Kuchuk, Natalia O; Viergever, Max A; van Laar, Jacob M; Vincken, Koen L; Lafeber, Floris P
Objectives To compare computerised and conventional methodology of radiographic joint destruction assessment in early rheumatoid arthritis (RA). Methods We investigated the contribution of the 3rd-to-5th carpometacarpal joints (CMC3-5, which are excluded in computerised assessment so far owing to bone overlapping) to total joint space narrowing (JSN) scores in two cohorts of patients with early RA (n=392). Next, we investigated agreement between JSN scoring using single time point individual joint-based method (individual joint of a single time point (IJSTP), reflecting computerised reading) and conventional JSN scoring using the Sharp-van der Heijde (SvdH) method in a cohort of patients with early RA (n=59). We used intraclass correlation coefficients (ICCs), Bland and Altman plots, and linear mixed modelling to analyse differences in progression between two methods. Radiographs were available at baseline, and at 1 and 2 years of follow-up. Results Of all joints affected by JSN at baseline or JSN progression during 2 years of follow-up, 3.9% and 6.6% concerned CMC3-5. Exclusion of CMC3-5 resulted in a decrease of 1.9–4.6% in JSN progression scores during 2 years of follow-up. The ICCs for JSN progression scores using IJSTP with or without CMC3-5 compared with SvdH were 0.71–0.81 and 0.69–0.78 at 1 and 2 years of follow-up. Signal-to-noise ratios for IJSTP-based and SvdH scoring were 0.51 and 0.58, respectively. The progression rate for each year was not statistically significantly different between two scoring methods (p=0.59 and 0.89). Conclusions This study showed that excluding CMC3-5 has limited influence on JSN (progression) scores and showed the feasibility of using IJSTP-based reading for computerised scoring of JSN (progression) in RA. PMID:26688750
de Santana, Frederico Santos; Nascimento, Dahan da Cunha; de Freitas, João Paulo Marques; Miranda, Raphaela Franco; Muniz, Luciana Feitosa; Santos Neto, Leopoldo; da Mota, Licia Maria Henrique; Balsamo, Sandor
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic symmetric polyarthritis of large and small joints and by morning stiffness that may lead to musculoskeletal impairment, with functional impotence. The concept of functionality relates to the ability of an individual to perform effectively and independently daily activities and tasks of everyday life. The aim of this review is to familiarize the rheumatologist with the concept of functional capacity evaluation and with the tests that can be applied in this population, as these are important steps for a proper exercise prescription. From functional tests already used in the elderly population, the Physical Fitness and Rheumatology Laboratory - LAR - Brasilia, which is accompanying patients from Brasilia Cohort of Early Rheumatoid Arthritis, describes in this article a protocol of tests to assess functional capacity for application in patients with RA, including the description of tests: 1) Sit and Reach; 2) Agility/Dynamic Balance; 3) Manual Dynamometry; 4) Sit Back and Lift; 5) Biceps Curl and 6) Six-minute Walk Test. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.
Passos Cardoso, André Luiz; Da Silva, Nilzio Antonio; Daher, Sérgio; De Moraes, Frederico Barra; Do Carmo, Humberto Franco
Objective: To evaluate the prevalence of cervical spine abnormalities among patients with rheumatoid arthritis and correlate the imaging findings with the clinical state. Methods: A cross-sectional study on 35 patients was carried out at the School of Medicine of the Federal University of Goiás (UFG) in 2004. The following were evaluated: age, use of medications and the clinical picture of pain and neurological characteristics. The erythrocyte sedimentation rate (ESR) and rheumatoid factor were tested, and radiographs of the cervical spine were produced in anteroposterior, lateral and dynamic views. To evaluate the influence of the variables on the emergence of instabilities, univariate and multivariate logistic regression tests were used (p < 0.05). Results: Among the 35 patients evaluated, 13 (37.1%) presented a stable cervical spine. Out of the 22 patients with instability, six presented more than one type. Atlantoaxial instability was found in 15 patients, with a mean anterior atlantodental distance of 3.40 mm in the neutral lateral radiographic view and 6.54 mm in the lateral view with flexion. Basilar invagination was found in five patients and subaxial subluxation in seven patients. Two thirds of the asymptomatic patients had instabilities. Bicipital hyperreflexia presented statistically significant correlations with atlantoaxial instability (p = 0.024) and subaxial instability (p = 0.01). Age at diagnosis correlated with subaxial instability (p = 0.02). Conclusions: The prevalence of cervical instability was 62.9 % (22/35). The most frequent instabilities were: atlantoaxial subluxation (42.9 %), subaxial subluxation (20%) and basilar invagination (14.3%). The correlation between instabilities and clinical signs and symptoms was poor. The patients with subaxial subluxation presented disease onset at a younger age. Dynamic radiography was important for diagnosing atlantoaxial subluxation. PMID:27022536
Bruera, Sebastian; Barbo, Andrea G; Lopez-Olivo, Maria A
Patients with rheumatoid arthritis (RA) often have difficulties adhering to their medical treatment plans. We determined the characteristics of patients with RA who used reminders and the association between reminders and adherence. A total of 201 patients with RA were asked the frequency of reminders use such as pill containers, calendars, or diaries. Patients completed self-reported adherence questionnaires, and their disease activity and functional ability were measured. Sixty-eight patients (34 %) reported using a reminder. Factors associated with reminder use were older age (yes-mean age 54 vs no-mean age 49, p = 0.004), race (Whites-54 % vs Blacks-30 % vs Hispanics-26 %, p = 0.003), and sex (males-50 % vs females 28 %, p = 0.005). Working patients were less likely to use reminders (employed-21 % vs unemployed-43 %, p = 0.006). Use of calendars was associated with adherence while away from home (ρ = 0.16, p = 0.03), when busy (ρ = 0.16, p = 0.03), and use of any reminder was associated with adherence when running out of pills (ρ = 0.15, p = 0.04). The use of calendar reminders was associated with fewer tender joints (ρ = -0.17, p = 0.02). Few patients with RA used reminders, and whites, males and patients of increasing age were most likely to use reminders. Our findings show that reminders can assist patients with RA in taking medications, particularly when they are most prone to forgetting, such as when they are away from home or busy. Providers should encourage using reminders as a low-cost aid to enhance adherence.