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  • Dual energy CT findings in gout with rapid kilovoltage-switching source with gemstone scintillator detector
    BMC Rheumatol. (IF 0) Pub Date : 2020-01-17
    Elin Svensson; Ylva Aurell; Lennart T. H. Jacobsson; Anton Landgren; Valgerdur Sigurdardottir; Mats Dehlin

    A definite diagnosis of gout requires demonstration of monosodium urate crystals in synovial fluid or in tophi, which in clinical practice today seldom is done. Dual energy CT (DECT) has repeatedly been shown to be able to detect monosodium urate crystals in tissues, hence being an alternative method to synovial fluid microscopy. The vast majority of these studies were performed with CT scanners with two X-ray tubes. In the present study we aim to investigate if and at what locations DECT with rapid kilovoltage-switching source with gemstone scintillator detector (GSI) can identify MSU crystals in patients with clinically diagnosed gout. We also performed a reliability study between two independent readings. Patients with new or established gout who had been examined with DECT GSI scanning of the feet at Sahlgrenska University Hospital, Mölndal between 2015 and 2018 were identified. Their medical records were sought for gout disease characteristics using a structured protocol. Urate deposits in MTP1, MTP 2–5, ankle/midfoot joints and tendons were scored semiquantatively in both feet and presence of artifacts in nail and skin as well as beam hardening and noise were recorded. Two radiologists performed two combined readings and scoring of the images, thus consensus was reached over the scoring at each occasion (Espeland et al., BMC Med Imaging. 2013;13:4). The two readings were compared with kappa statistics. DECT GSI could identify urate deposits in the feet of all 55 participants with gout. Deposits were identified in the MTP-joints of all subjects but were also present in ankle/midfoot joints and tendons in 96 and 75% respectively. Deposition of urate was predicted by longer disease duration (Spearman’s Rho 0.64, p < .0001) and presence of tophi (p = 0.0005). Artifacts were common and mostly found in the nails (73%), a minority displayed skin artifacts (31%) while beam hardening and noise was rare. The agreement between the two readings was good (Κ = 0.66, 95% CI = 0.61–0.71). The validity of DECT GSI in gout is supported by the identification of urate in all patients with clinical gout and the good correlations with clinical characteristics. The occurrence of artifacts was relatively low with expected locations.

  • Patients’ perspectives of outcomes after total knee and total hip arthroplasty: a nominal group study
    BMC Rheumatol. (IF 0) Pub Date : 2020-01-13
    Susan M. Goodman; Bella Mehta; Serene Z. Mirza; Mark P. Figgie; Michael Alexiades; Jose Rodriguez; Peter Sculco; Michael Parks; Jasvinder A. Singh

    While total joint replacements (TJR) are frequently performed, there is little qualitative research to define the outcomes most important to patients. Patients who had received total hip (THR) or total knee replacements (TKR) participated in 8 nominal groups to answer the question “What result/results matter the most to a patient undergoing/having a knee or hip replacement?” Total 270 votes were allocated. Eight nominal groups were performed with 45 patients, 6 groups with mean age (71.1 ± 9.3), and 2 with 9 younger patients (mean age 36.8 ± 7.4). All had TJR between 2016 and 2018; overall, 40% were male, 15.6% were Black, and 75% were performed for osteoarthritis. While all groups ranked the same top 3 outcomes, responses varied with age: 1) relief of pain (46% vs. 35% in the young groups); 2) improved function including mobility (29% vs. 18% in the young groups); 3) restored quality of life (13% vs 33% of votes in the younger group). Relief of pain and restoration of function, and improved quality of life are the 3 outcomes ranked highest by patients, confirming their inclusion in TJR clinical trials.

  • Patient perspectives on the pathway to psoriatic arthritis diagnosis: results from a web-based survey of patients in the United States
    BMC Rheumatol. (IF 0) Pub Date : 2020-01-10
    Alexis Ogdie; W. Benjamin Nowell; Eddie Applegate; Kelly Gavigan; Shilpa Venkatachalam; Marie de la Cruz; Emuella Flood; Ethan J. Schwartz; Beverly Romero; Peter Hur

    There are limited real-world data on the diagnostic experiences of patients with psoriatic arthritis (PsA), including medical care sought and potential barriers to diagnosis. We aim to describe patient experiences related to receiving a PsA diagnosis. Ours was a mixed-method, 2-phase study. Phase 1 comprised concept elicitation and cognitive interviews with clinical experts and adults diagnosed with PsA to develop a cross sectional, web-based survey. US adults with a self-reported PsA diagnosis were recruited through a patient support community (CreakyJoints), an online patient research registry (ArthritisPower), and social media outreach. In Phase 2, the online survey collected data on sociodemographics, clinical symptoms, disease burden, and diagnosis history of survey respondents with PsA. Of the 203 respondents included, 172 (84.7%) were female, and the mean (SD) age was 51.6 (10.8) years. The time between seeking medical attention and receiving a diagnosis was < 6 months for 69 respondents, 6 months to 4 years for 68 respondents, and ≥ 5 years for 66 respondents. Most respondents sought care from general practitioners (79.8%) and rheumatologists (66.5%). Common initial symptoms that led respondents to seek medical attention were joint pain (70.0%) and stiffness (53.7%). Among the initial symptoms that led respondents to seek care, joint pain, swollen joints, and sausage-like fingers or toes (indicating dactylitis) were more common among respondents with shorter time to diagnosis, whereas stiffness, fatigue, enthesitis (indicated by foot problems, tendon and ligament pain), and back pain were more common among respondents with longer time to diagnosis. Common misdiagnoses were psychosomatic issues (26.6%) and osteoarthritis (21.7%). Respondents with shorter times to diagnosis had lower frequencies of misdiagnosis. Respondents with PsA reported delays in diagnosis and misdiagnoses on their journey to a PsA diagnosis. Symptom differences, such as enthesitis and stiffness, were noted among respondents with shorter vs longer time to diagnosis. Increased understanding of diagnostic barriers may lead to earlier diagnosis and appropriate management to improve outcomes.

  • Factors that influence rheumatologists’ anti-tumor necrosis factor alpha prescribing decisions: a qualitative study
    BMC Rheumatol. (IF 0) Pub Date : 2019-12-19
    Sean P. Gavan; Gavin Daker-White; Katherine Payne; Anne Barton

    Treatment decisions for any disease are usually informed by reference to published clinical guidelines or recommendations. These recommendations can be developed to improve the relative cost-effectiveness of health care and to reduce regional variation in clinical practice. Anti-tumor necrosis factor alpha (anti-TNF) treatments are prescribed for people with rheumatoid arthritis according to specific recommendations by the National Institute for Health and Care Excellence in England. Evidence of regional variation in clinical practice for rheumatoid arthritis may indicate that different factors have an influence on routine prescribing decisions. The aim of this study was to understand the factors that influence rheumatologists’ decisions when prescribing anti-TNF treatments for people with rheumatoid arthritis in England. Semi-structured one-to-one telephone interviews were performed with senior rheumatologists in different regions across England. The interview schedule addressed recommendations by the National Institute for Health and Care Excellence, prescribing behavior, and perceptions of anti-TNF treatments. Interviews were recorded digitally, transcribed verbatim, and anonymized. Data were analyzed by thematic framework analysis that comprised six stages (familiarization; coding; developing the framework; applying the framework; generating the matrix; interpretation). Eleven rheumatologists (regional distribution - north 36%; midlands: 36%; south: 27%) participated (response rate: 24% of the sampling frame). The mean duration of the interviews was thirty minutes (range: 16 to 56 min). Thirteen factors that influenced anti-TNF prescribing decisions were categorized by three nested primary themes; specific influences were defined as subthemes: (i) External Environment Influences (National Institute for Health and Care Excellence Recommendations; Clinical Commissioning Groups; Cost Pressures; Published Clinical Evidence; Colleagues in Different Hospitals; Pharmaceutical Industry); (ii) Internal Hospital Influences (Systems to Promote Compliance with Clinical Recommendations; Internal Treatment Pathways; Hospital Culture); (iii) Individual-level Influences (Patient Influence; Clinical Autonomy; Consultant Experience; Perception of Disease Activity Score-28 (DAS28) Outcome). Factors that influenced anti-TNF prescribing decisions were multifaceted, seemed to vary by region, and may facilitate divergence from published clinical recommendations. Strategic behavior appeared to illustrate a conflict between uniform treatment recommendations and clinical autonomy. These influences may contribute to understanding sources of regional variation in clinical practice for rheumatoid arthritis.

  • Serum levels of reactive oxygen metabolites at 12 weeks during tocilizumab therapy are predictive of 52 weeks-disease activity score-remission in patients with rheumatoid arthritis
    BMC Rheumatol. (IF 0) Pub Date : 2019-12-16
    Arata Nakajima; Keiichiro Terayama; Masato Sonobe; Yasuchika Aoki; Hiroshi Takahashi; Yorikazu Akatsu; Junya Saito; Shinji Taniguchi; Manabu Yamada; Ayako Kubota; Koichi Nakagawa

    To verify whether serum levels of reactive oxygen metabolites (ROM) are predictive of future clinical remission in patients with rheumatoid arthritis (RA) receiving tocilizumab (TCZ) therapy. A total of 46 patients with RA receiving TCZ therapy were enrolled in this study. Patients were divided into remission and non-remission groups based on disease activity score 28 (DAS28)-erythrocyte sedimentation rate (ESR) or clinical disease activity index (CDAI) at 52 weeks. Associations between serum levels of ROM, C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3) at 4 and 12 weeks and the remission by DAS28-ESR and CDAI at 52 weeks were investigated. There were no significant differences in CRP and MMP-3 between DAS- or CDAI-remission and non-remission groups at 12 weeks. However, ROM in DAS-remission group were significantly lower than those in the non-remission group. For ROM, the area under the curve of the receiver operating characteristic curve was 0.735 and the cut-off value that distinguished DAS-remission group from non-remission group was 305.5 U. Carr (sensitivity: 70.0%, specificity: 72.2%). A multivariate logistic regression analysis revealed that ROM at 12 weeks was associated with DAS-remission at 52 weeks (odds ratio: 6.067, 95% confidence interval: 1.305–28.203). Serum levels of ROM at 12 weeks during TCZ therapy may be predictive of DAS-remission at 52 weeks in patients with RA.

  • Use of a “critical difference” statistical criterion improves the predictive utility of the Health Assessment Questionnaire-Disability Index score in patients with rheumatoid arthritis
    BMC Rheumatol. (IF 0) Pub Date : 2019-12-10
    Frank Behrens; Michaela Koehm; Eva C. Schwaneck; Marc Schmalzing; Holger Gnann; Gerd Greger; Hans-Peter Tony; Harald Burkhardt

    The Health Assessment Questionnaire-Disability Index (HAQ-DI) is used to assess functional status in rheumatoid arthritis (RA), but the change required for meaningful improvements remains unclear. A minimum clinically important difference (MCID) of 0.22 is frequently used in RA trials. The aim of this study was to determine a statistically defined critical difference for HAQ-DI (HAQ-DI-dcrit) and evaluate its association with therapeutic outcomes. We retrospectively analyzed data from adult German patients with RA enrolled in a multicenter observational trial in which they received adalimumab therapy at the decision of the treating clinician during routine clinical care. The HAQ-DI-dcrit, defined as the minimum change that can be reliably discriminated from random long-term variations in patients on stable therapy, was determined by evaluating intra-individual variation in patient scores. Other outcomes of interest included Disease Activity Score-28 joints and patient-reported pain and fatigue. The HAQ-DI-dcrit was calculated as an improvement (decrease) from baseline of 0.68 in a discovery cohort (N = 1645) of RA patients on stable therapy and with moderate disease activity (mean DAS28 [standard deviation] of 4.4 [1.6]). In the full patient cohort (N = 2740), 22.1% of patients achieved a HAQ-DI-dcrit improvement at month 6. Compared with patients with a small improvement in HAQ-DI (decrease of ≥0.22 to < 0.68) or no improvement (< 0.22), patients achieving a HAQ-DI-dcrit at month 6 had better therapeutic outcomes at months 12 and 24, including stable functional improvements. Change in pain was the most important predictor of HAQ-DI improvement during the first 6 months of therapy. A HAQ-DI-dcrit of 0.68 is a reliable measure of functional improvement. This measure may be useful in routine clinical care and clinical trials. ClinicalTrials.gov NCT01076205. Registered on February 26, 2010 (retrospectively registered).

  • Fibroblast-like synovial cell production of extra domain A fibronectin associates with inflammation in osteoarthritis
    BMC Rheumatol. (IF 0) Pub Date : 2019-12-02
    Tue W. Kragstrup; Dong H. Sohn; Christin M. Lepus; Kazuhiro Onuma; Qian Wang; William H. Robinson; Jeremy Sokolove

    The pathophysiology of osteoarthritis (OA) involves wear and tear, and a state of low-grade inflammation. Tissue repair responses include transforming growth factor beta (TGFβ)-induced myofibroblast production of extracellular matrix. Fibronectins are an essential part of the extracellular matrix, and injection of fibronectin fragments into rabbit joints is a previously established animal model of OA. Fibronectin containing the ED-A domain is currently being used as drug delivery target in the development of anti-inflammatory drugs (e.g. Dekavil). In this study, samples of synovial membrane were obtained from patients with knee OA undergoing joint replacement surgery. Immunostaining for ED-A fibronectin and the myofibroblast marker alpha smooth muscle actin (αSMA) was performed on fibroblast-like synovial cells (FLS) and synovial membranes. RAW 264.7 macrophages were incubated with recombinant ED-A fibronectin. The staining of ED-A fibronectin in OA FLS was increased by TGFβ but not by TNFα, lipopolysaccharide, or IL-6 (n = 3). ED-A fibronectin co-stained with the myofibroblast marker αSMA in both the OA FLS (n = 3) and in the OA synovial membranes (n = 8). ED-A fibronectin staining was associated with both number of lining layer cells (rho = 0.85 and p = 0.011) and sublining cells (rho = 0.88 and p = 0.007) in the OA synovium (n = 8), and co-distributed with TNFα (n = 5). Recombinant ED-A fibronectin increased the production of TNFα by RAW 264.7 macrophages (n = 3). The disease process in OA shares features with the chronic wound healing response. Our findings support utilizing ED-A fibronectin for drug delivery or therapeutic targeting to reduce pro-inflammatory responses in OA.

  • Positive melioidosis serology in a patient with adult onset Still’s disease: a case report of a diagnostic dilemma
    BMC Rheumatol. (IF 0) Pub Date : 2018-12-10
    Harsha Anuruddhika Dissanayake; Gayani Premawansa; Enoka Corea; Inoshi Atukorale

    Autoimmune disorders are known to produce false positives in serological tests for infections. Aetiological association between infections and autoimmunity, increased susceptibility to infectious and autoimmune disorders with immune dysregulation and non-specific polyclonal expansion of B cells with autoimmunity may cause confusion in diagnosis and patient management. We report a patient with Adult Onset Still’s Disease (AOSD) presenting with rising melioidosis antibody titres that caused diagnostic confusion. A forty-nine-year-old female presented with prolonged fever, sore-throat, large joint arthritis, lymphadenopathy, hepatomegaly and transient rash. She had elevated inflammatory markers and a rising melioidosis antibody titre. The patient responded poorly to prolonged course of appropriate antimicrobials but showed rapid and sustained improvement with glucocorticoids. Positive melioidosis serology could have been due to a co-infection or false positive antibody reaction due to non-specific B cell expansion or an indicator of true infection that triggered the immune dysregulation to develop AOSD.

  • Association of Catechol-O-methyltransferase single nucleotide polymorphisms, ethnicity, and sex in a large cohort of fibromyalgia patients
    BMC Rheumatol. (IF 0) Pub Date : 2018-12-12
    Chee Lee; Ginevra Liptan; Svetlana Kantorovich; Maneesh Sharma; Ashley Brenton

    Fibromyalgia (FM) is a complex, centralized pain condition that is often difficult to diagnose and treat. FM is considered to have a genetic background due to its familial aggregation and due to findings from multiple candidate-gene studies implicating catecholaminergic and serotonergic neurotransmitter systems in chronic pain. However, a multi-factorial analysis of both genetic and environmental risk factors is lacking. A better characterization of the interplay of risk factors may assist in understanding the pathophysiology of FM, its clinical course, and assist in early diagnosis and treatment of the disorder. This retrospective study included 60,367 total participants from 237 clinics across the USA. Of those, 2713 had been diagnosed with fibromyalgia, as indicated by ICD code. Logistic regression was used to test for associations of diagnosed FM in study subjects with COMT SNPs and COMT haplotypes, which were previously found to be linked with pain sensitivity, as well as demographics such as age, sex, and ethnicity. The minor allele frequencies of COMT SNPs in the FM population were compared with 1000 Genomes data using a χ2 test to determine significant deviations from the estimated population allelic frequencies. FM diagnosis was strongly associated with sex, age, and ethnicity. Females, those between 49 and 63 years, and non-Caucasians were at higher risk of FM. Females had 1.72 increased odds of FM (p = 1.17 × 10− 30). African-Americans were 1.52 times more likely to have a diagnosis of FM compared to Caucasians (p = 3.11 × 10− 12). Hispanics were less likely to have a diagnosis of FM compared to Caucasians (p = 3.95 × 10− 7). After adjusting for sex and ethnicity, those in the low age group and mid age group had 1.29 (p = 1.02 × 10− 5) and 1.60 (p = 1.93 × 10− 18) increased odds of FM, respectively, compared to the high age group, where age was categorized by tertile (low (< 49), mid (49–63), and high (> 63)). The COMT haplotypes associated with pain sensitivity were not associated with FM, but African-Americans were 11.3 times more likely to have a high pain sensitivity COMT diplotype, regardless of FM diagnosis. However, the minor alleles of COMT SNPs rs4680, rs4818, rs4633 and rs6269 were overrepresented in the FM population overall, and varied when compared with ethnically-similar populations from 1000 Genomes. This is the largest study, to date, that examines demographic and genetic associations of FM in a diverse population. While pain sensitivity-associated COMT haplotypes were not found to be directly associated with FM diagnosis, the minor alleles that make up the COMT haplotypes were overrepresented in the FM population, suggesting a role of COMT in FM. Future studies are needed to elucidate the exact role of COMT variation in widespread pain conditions, such as FM. Clinically, this information can be used to provide insight into the pathways underlying FM and to identify those at greater risk of developing FM.

  • Malignancy risk in Australian rheumatoid arthritis patients treated with anti-tumour necrosis factor therapy: an update from the Australian Rheumatology Association Database (ARAD) prospective cohort study
    BMC Rheumatol. (IF 0) Pub Date : 2019-01-08
    Margaret P. Staples; Lyn March; Catherine Hill; Marissa Lassere; Rachelle Buchbinder

    Tumour necrosis factor inhibitor (TNFi) therapy has been available for rheumatoid arthritis (RA) patients for several decades but data on the long-term risk of malignancy associated with its use is limited. Our aims were to assess malignancy risk in a cohort of Australian RA patients relative to the Australian population and to compare cancer risk for patients exposed to TNFi therapy versus a biologic-naïve group. Demographic data for RA participants enrolled in the Australian Rheumatology Association Database (ARAD) before 31 Dec 2012 were matched to national cancer records in May 2016 (linkage complete to 2012). Standardised incidence ratios (SIRs) were used to compare malignancy incidence in TNFi-exposed and biologic-naïve ARAD participants with the Australian general population using site-, age- and sex-specific rates by calendar year. Malignancy incidence in TNFi-exposed participants and biologic-naïve RA patients, were compared using rate ratios (RRs), adjusted for age, sex, smoking, methotrexate use and prior malignancy. There were 107 malignancies reported after 10,120 person-years in the TNFi-exposed group (N = 2451) and 49 malignancies after 2232 person-years in the biologic-naïve group (N = 574). Compared with the general population, biologic-naïve RA patients showed an increased risk for overall malignancy (SIR 1.52 (95% confidence interval (CI) 1.16, 2.02) prostate cancer (SIR 2.10, 95% CI 1.18, 4.12). The risk of lung cancer was increased for both biologic naïve and TNFi-exposed patients compared with the general population (SIR 2.69 (95% CI 1.43 to 5.68) and SIR 1.69 (95% CI 1.05 to 2.90) respectively). For the TNFi-exposed patients there was an increased risk of lymphoid cancers (SIR 1.82, 95% CI 1.12, 3.18). There were no differences between the exposure groups in the risk of cancer for any of the specific sites examined. Overall malignancy incidence was elevated for biologic-naïve RA patients but not for those exposed to TNFi. TNFi exposure did not increase malignancy risk beyond that experienced by biologic-naïve patients. Lung cancer risk was increased for both TNFi-treated and biologic-naïve RA patients compared with the general population suggesting that RA status or RA treatments other than TNFi may be responsible in some way.

  • Effectiveness and cost-effectiveness of the modified Pilates method versus aerobic exercise in the treatment of patients with fibromyalgia: protocol for a randomized controlled trial
    BMC Rheumatol. (IF 0) Pub Date : 2019-01-18
    Katherinne Ferro Moura Franco; Yuri Rafael dos Santos Franco; Evany Maira Espírito Santo Salvador; Bruna Cristina Brajon do Nascimento; Gisela Cristiane Miyamoto; Cristina Maria Nunes Cabral

    Fibromyalgia is characterized by chronic generalized pain, fatigue, sleep disorders and other symptoms. Physical exercise is recommended as the first choice of non-pharmacological therapy. Thus, the aim of this study is to evaluate the effectiveness and cost-effectiveness of modified Pilates exercises compared to aerobic exercises in the treatment of patients with fibromyalgia. In this randomized controlled trial with blinded assessor, 98 patients who meet the fibromyalgia classification criteria of the American College of Rheumatology 2010, aged between 20 and 75 years, and with pain intensity greater than or equal to 3 points in the Pain Numerical Rating Scale, will be randomly divided into Aerobic Group (aerobic exercises on treadmills or stationary bikes) and Pilates Group (modified Pilates exercises), and treated twice a week for eight weeks on the Center for Excellence in Clinical Research in Physical Therapy at Universidade Cidade de São Paulo, Brazil. The following outcomes will be evaluated by a blinded assessor at baseline, eight weeks, six months, and 12 months after randomization: impact of fibromyalgia assessed by the Fibromyalgia Impact Questionnaire, pain intensity by the Pain Numerical Rating Scale, kinesiophobia by the Tampa Scale of Kinesiophobia, specific disability by the Patient-Specific Functional Scale, functional capacity by the 6-min Walk Test, quality of sleep by the Pittsburgh Sleep Quality Index, and health-related quality of life by EQ-5D-3L and SF-6D questionnaires. It is expected that the Pilates exercises will be more effective than aerobic exercises in improving clinical outcomes and that this improvement will be maintained over the medium to long term. This study aims to clarify whether the Pilates method can be incorporated into the clinical practice of physical therapists treating patients with fibromyalgia. The study will also provide information on which exercise will be most cost-effective, information that can be used by insurers and public health systems. This study was prospectively registered at the Clinical Trials Registry ( NCT03050606 ) in February 2017.

  • Tissue metabolite of type I collagen, C1M, and CRP predicts structural progression of rheumatoid arthritis
    BMC Rheumatol. (IF 0) Pub Date : 2019-01-31
    Anne C. Bay-Jensen; Adam Platt; Martin A. Jenkins; Michael E. Weinblatt; Inger Byrjalsen; Kishwar Musa; Mark C. Genovese; Morten A. Karsdal

    Biomarkers of rheumatoid arthritis (RA) disease activity typically measure inflammation or autoimmunity (e.g. CRP, RF). C1M and C3M, metabolites of type I and III collagen, are markers reflecting tissue metabolism. These markers have been documented to provide additional prognostic and predictive value compared to commonly used biomarkers. We investigated the relationship of high serum levels of C1M or C3M to radiographic progression, and benchmarked them to CRP and RF. Placebo treated patients of the OSK1, 2 and 3 studies (Phase III clinical trials testing efficacy of fostamatinib) with baseline serum biomarkers C1M, C3M, CRP and RF were included (nBL = 474). Van der Heijde mTSS was calculated at baseline and 24-week (n24 = 261). Progression was defined as moderate or rapid by ΔmTSS ≥0.5 or ≥ 5 units/year. Patients were divided into subgroups; low (L), high (H) or very high (V) C1M, C3M and CRP, or RF negative, positive and high positive. Difference in clinical parameters were analyzed by Mann-Whitney or χ2tests, and modelling for prediction of progression by logistic regression including covariates (age, gender, BMI, and clinical assessment scores). Levels of C1M, C3M, CRP and RF were significantly (p < 0.05) associated with measures of disease activity and mTSS at baseline. For prognostic measures, there were 2.5 and 4-fold as many rapid progressors in the C1MH and CRPH (p < 0.05), and in the C1MV and CRPV groups (p < 0.001) compared C1ML and CRPL, respectively. C1M and CRP performed similarly in the predictive analysis, where high levels predicted moderate and rapid progression with odds ratio of 2.1 to 3.8 and 3.7 to 13.1 after adjustment for covariates. C3M and RF did not provide prognostic value alone. Serum C1M and CRP showed prognostic value and may be tools for enrichment of clinical trials with structural progressor. The two markers reflect two different aspect of disease pathogenesis (tissue turnover vs. inflammation), thus may provide individual and supplementary information.

  • Living life precariously with rheumatoid arthritis - a mega-ethnography of nine qualitative evidence syntheses
    BMC Rheumatol. (IF 0) Pub Date : 2019-02-06
    Fran Toye; Kate Seers; Karen Louise Barker

    Rheumatoid arthritis is an autoimmune disease that causes joint inflammation. It affects around 400,000 people in the UK and 1 million adults in the USA. Given the appropriate treatment, many can have relatively few symptoms. It is therefore important to understand what it is like to live with rheumatoid arthritis and gain insight into peoples’ decisions about utilising healthcare. The aims of this study were: (1) to bring together qualitative evidence syntheses that explore patients’ experience of living with rheumatoid arthritis and (2) develop a conceptual understanding of what it is like to live with rheumatoid arthritis. We used the methods of mega-ethnography. The innovation of mega-ethnography is to use conceptual findings from qualitative evidence syntheses as primary data. We searched four bibliographic databases from inception until September 2018 to identify qualitative evidence syntheses that explored patients’ experience of rheumatoid arthritis. We identified 373 qualitative evidence syntheses, removed 179 duplicates and screened 194 full text studies. We identified 42 qualitative evidence syntheses that explored the experience of pain or arthritis and 9 of these explored the experience of rheumatoid arthritis. We abstracted ideas into 10 conceptual categories: (1) rheumatoid arthritis is in control of my body (2) rheumatoid arthritis alters reciprocity; (3) rheumatoid arthritis is an emotional challenge; (4) rheumatoid arthritis disrupts my present and future self; (5) the challenge of balancing personal and work life; (6) I am trying to make sense of what is happening; (7) rheumatoid arthritis is variable and unpredictable; (8) rheumatoid arthritis is invisible; (9) I need a positive experience of healthcare, and (10) I need to reframe the situation. We developed a conceptual model underpinned by living life precariously with rheumatoid arthritis. This is the second mega-ethnography, or synthesis of qualitative evidence syntheses using the methods of meta-ethnography. Future research should consider the proliferation of qualitative evidence synthesis in order to avoid duplication of research effort. Our model for rheumatoid arthritis has some important clinical implications that might be transferable to other musculoskeletal conditions.

  • Severe skin disease in lupus associated with hemophagocytic lymphohistiocytosis: case reports and review of the literature
    BMC Rheumatol. (IF 0) Pub Date : 2019-02-08
    Christina S. Thornton; Parham Minoo; Michelle Schneider; Aurore Fifi-Mah

    Hemophagocytic lymphohistiocytosis (HLH) is a severe clinical entity associated with high mortality in the adult population. HLH has been associated with infections, malignancy and autoimmune conditions such as Systemic Lupus Erythematosus (SLE), however this is often in the context of a disease flare. Currently, there are limited reports of inaugural SLE manifesting as HLH with a lack of consensus on treatment and management of these patients. Here, we present two rare case reports of severe cutaneous manifestation of lupus associated with HLH. Both patients presented with sinister clinical courses with primarily rheumatologic complaints including malaise, arthralgia, and myalgia with biochemical abnormalities. Both patients were diagnosed with HLH as a result of first presentation from cutaneous lupus. A comprehensive literature review using the PubMed database with cases comprising keywords of HLH and SLE up to September 2017 was conducted, with an emphasis on inaugural cutaneous SLE cases. Ultimately, we highlight that a keen clinical acumen is required as misdiagnosis may lead to insufficient treatment with adverse clinical outcomes with the unique presentation of HLH from inaugural cases of SLE.

  • Real world long-term impact of intensive treatment on disease activity, disability and health-related quality of life in rheumatoid arthritis
    BMC Rheumatol. (IF 0) Pub Date : 2019-02-25
    Nicola J. Gullick; Fowzia Ibrahim; Ian C. Scott; Alexandra Vincent; Andrew P. Cope; Toby Garrood; Gabriel S. Panayi; David L. Scott; Bruce W. Kirkham

    The emphasis on treating rheumatoid arthritis (RA) intensively reduces disease activity but its impact in routine care is uncertain. We evaluated temporal changes in disease activities and outcomes in a 10-year prospective observational cohort study of patients in routine care at one unit. The Guy’s and St Thomas’ RA cohort was established in 2005. It involved most RA patients managed in this hospital. Clinical diagnoses of RA were made by rheumatologists. Patients were seen regularly in routine care. Each visit included measurement of disease activity scores for 28 joints (DAS28), health assessment questionnaire scores (HAQ) and EuroQol scores. Patients received intensive treatments targeting DAS28 remission. In 1693 RA patients mean DAS28 scores fell from 2005 to 15 by 11% from 4.08 (95% CI: 3.91, 4.25) in 2005 to 3.64 (3.34, 3.78); these falls were highly significant (p < 0.001). DAS28 components: swollen joint counts fell by 32% and ESR by 24%; in contrast tender joint counts and patient global assessments showed minimal or no reductions. The reduction in DAS28 scores was predominantly between 2005 and 2010, with no falls from 2011 onwards. Associated with falls in mean DAS28s, patients achieving remission increased (18% in 2005; 27% in 2015) and the number with active disease (DAS28 > 5.1) decreased (25% in 2005; 16% in 2015). In 752 patients seen at least annually for 3 years, persisting remission (68 patients) and intermittent remission (376 patients) were associated with less disability and better health related quality of life. Over time biologic use increased, but they were used infrequently in patients in persistent remission. Over 10 years an intensive management strategy in a routine practice setting increased combination DMARD and biologic use: disease activity levels declined; this association is in keeping with a causal relationship. Patients who achieved remission, even transiently, had better functional outcomes than patients never achieving remission.

  • Comparative study of Interleukin-18 (IL-18) serum levels in adult onset Still’s disease (AOSD) and systemic onset juvenile idiopathic arthritis (sJIA) and its use as a biomarker for diagnosis and evaluation of disease activity
    BMC Rheumatol. (IF 0) Pub Date : 2019-02-28
    Holger Kudela; Susanne Drynda; Anke Lux; Gerd Horneff; Joern Kekow

    Signs and symptoms establish the diagnosis of adult onset Still’s disease (AOSD) as well as of systemic onset juvenile idiopathic arthritis (sJIA). The published data regarding the importance of IL-18 as a marker for diagnosis and disease activity so far are conflicting. The aim of this study was to clarify the role of IL-18 as a diagnostic and disease activity marker in AOSD and sJIA. Thirty adult patients diagnosed with AOSD and twenty children diagnosed with sJIA were included in the study. Clinical and laboratory data were obtained retrospectively for each patient visit whenever IL-18 serum levels were determined. IL-18 levels were determined by ELISA. Sixty-five adults and twenty-three children presenting with fever and/or arthritis who did not meet the criteria for a diagnosis of AOSD or sJIA served as comparison groups. Rau’s criteria and CRP values were used to evaluate disease activity. IL-18 levels were significantly elevated in patients with active AOSD compared to AOSD patients in remission and to the comparison group with a median of 16,327 pg/ml, 470 pg/ml, and 368 pg/ml, respectively (p < 0.001). Analogous to AOSD in active sJIA, the median IL-18 serum level was significantly higher with 21,512 pg/ml than in the comparison group with 2580 pg/ml (p < 0.001). At our cut-off point of 5000 pg/ml, the calculated specificity of IL-18 to establish the diagnosis of AOSD was 96.9%, and the sensitivity 63.3% (AUC = 0.870, p < 0.001). For the diagnosis of sJIA, a cut-off value of 10,000 pg/ml was chosen with a specificity of 100% and a sensitivity of 60% (AUC = 0.774, p = 0.003). At a cut-off value of 5000 pg/ml, the specificity was 62% and the sensitivity 65%. This study gives further evidence to earlier publications of elevated IL-18 serum levels in active AOSD and sJIA, with up to 1000-fold higher concentrations compared to other rheumatic diseases. A clear association of IL-18 serum levels with disease activity in AOSD was found. The results support the use of IL-18 as an important biomarker in AOSD and sJIA.

  • Gout and sexual function: patient perspective of how gout affects personal relationships and intimacy
    BMC Rheumatol. (IF 0) Pub Date : 2019-02-28
    Jasvinder A. Singh

    In absence of previous studies, we assessed how gout impacts relationship and intimacy with spouse/significant other. We enrolled a convenience sample of consecutive patients with doctor-diagnosed gout from a community-based outpatient clinic. Nominal groups were conducted until saturation was achieved. Responses were collected verbatim, discussed and then rank-ordered by each participant with votes. Forty-four patients with gout participated in 14 nominal groups, seven male only groups, six female only groups and one group had people with both sexes. Overall, the mean age was 61.7 years (SD, 12.2), mean gout duration was 11.8 years (SD, 11.8), 50% were men, 68% African-American, 43% retired, 48% currently married, 94% were using either allopurinol and/or febuxostat, and 39% had had no gout flares in the last 6 months. The top five responses accounted for 75% of all votes and included physical (28%) or emotional impact (17.4%) on intimacy, disability (12.9%), issues with trust/understanding (10.6%) and social life interference (6.8%). When examining the top-rated concern for each nominal group, physical impact on intimacy was ranked top by eight nominal groups; and emotional impact on intimacy, physical function limitation, trust issues/understanding by two nominal groups each. There were no differences evident by patient gender in the concern that was top-ranked. Gout significantly impacts relationship and intimacy with spouse/significant other. Our observation of the physical and emotional impact of gout on intimacy should lead to studies to understand this further and assess if more optimal gout control can improve sex lives of people with gout.

  • Eosinophils in anti-neutrophil cytoplasmic antibody associated vasculitis
    BMC Rheumatol. (IF 0) Pub Date : 2019-03-08
    Thomas Hellmark; Sophie Ohlsson; Åsa Pettersson; Markus Hansson; Åsa C. M. Johansson

    Anti-neutrophil cytoplasmic antibodies associated vasculitides (AAV) are characterized by autoimmune small vessel inflammation. Eosinophils are multifunctional cells with both pro-inflammatory and immunoregulatory properties. Tissue activated eosinophils secrete cyto- and chemokines and form extracellular traps (EETs), they release free granules and produce reactive oxygen species. The role of eosinophils is well established in eosinophilic granulomatosis with polyangiitis (EGPA) but very little is known about their role in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). The expression of surface markers CD11c, CD11b, CD16, CD35, CD62L, CD64, CD88, Siglec-8 and CD193 and reactive oxygen species production by peripheral blood eosinophils were studied using flow cytometry. Fluorescence microscopy was used to visualize the release of eosinophil extracellular DNA traps (EETs). 98 GPA and MPA patients and 121 healthy controls were included in the study. Both GPA and MPA patients had decreased frequency of eosinophils in peripheral blood compared with healthy controls (p < 0.0001), which could not solely be explained by corticosteroid treatment. The patient’s eosinophils showed increased surface expression of the Fc receptors CD16 (p < 0.0001) and CD64 (p = 0.0035) as well as CCR3 (CD193) (p = 0.0022). Decreased expression was found of the complement receptors CD35 (p = 0.0022), CD88 (p < 0,0001) as well as CD11c (p < 0,0001), CD11b (p = 0.0061) and Siglec-8 (p = 0,0015). Moreover, GPA and MPA eosinophils, showed decreased capacity to produce ROS (p < 0.0001). ANCA stimulation of eosinophils from GPA and MPA patients after C5a priming enhanced EETosis (p = 0,0088). The percentage of eosinophils were decreased in peripheral blood in GPA and MPA patients and showed altered surface marker expression and function. The enhanced EETosis after ANCA stimulation, suggests that eosinophil can contribute to the autoantibody driven inflammatory process.

  • Relapse rates after elective discontinuation of anti-TNF therapy in rheumatoid arthritis: a meta-analysis and review of literature
    BMC Rheumatol. (IF 0) Pub Date : 2019-03-08
    Arduino A. Mangoni; Fahdah Al Okaily; Hani Almoallim; Seham Al Rashidi; Reem Hamdy A. Mohammed; Amal Barbary

    Inhibitors of tumor necrosis factor alpha (TNF-α) are current mainstay of therapies for rheumatoid arthritis (RA). The decision when to withdraw TNF-α inhibitors after achieving remission and the incidence of relapse rates with elective discontinuation are both important questions that demand intense survey in these patients. In this meta-analysis we aimed to estimate the magnitude of relapse rate after elective TNF-α inhibitor discontinuation in RA patients with remission. Systematic searches of PubMed/MEDLINE, Cochrane Library databases, grey literature (unpublished and ongoing trials) from the WHO International Clinical Trials Registry Platform and the US National Institutes of Health were performed for studies reporting the outcomes of elective discontinuation of TNF-α inhibitor in RA patients after remission. Random-effects models for meta-analyses were conducted on extracted data. Out of 390 references screened, 16 RCTs were included. Meta-analysis of 1264 patient data revealed a relapse rate of 0.47 (95% CI 0.41–0.54). Sensitivity analysis showed that none of the studies had higher influence on the results. Almost half of all the RA patients in remission relapse after elective TNF-α inhibitor discontinuation. This information might be useful when considering this management option with individual patients.

  • Incident gout and chronic Kidney Disease: healthcare utilization and survival
    BMC Rheumatol. (IF 0) Pub Date : 2019-03-19
    Dena H. Jaffe; Alyssa B. Klein; Arriel Benis; Natalia M. Flores; Hagit Gabay; Robert Morlock; Dana Y. Teltsch; Jonathan Chapnick; Yair Molad; Shmuel M. Giveon; Becca Feldman; Maya Leventer-Roberts

    Uncontrolled gout can cause significant joint and organ damage and has been associated with impairments in quality of life and high economic cost. Gout has also been associated with other comorbid diseases, such as chronic kidney disease. The current study explored if healthcare resource utilization (HRU) and survival differs between patients with incident gout in the presence or absence of chronic kidney disease (CKD). Clalit Health Services (CHS) data were used to conduct a retrospective population-based cohort study of incident gout between 1/1/2006–31/12/2009. Incident cases of gout were identified and stratified by CKD status and by age group (< 55 and 55+ years). CKD status was defined as a pre-existing diagnosis of chronic kidney disease, chronic renal failure, kidney transplantation, or dialysis at index date. Demographic and clinical characteristics, as well as healthcare resource use, were reported. A total of 12,940 incident adult gout patients, with (n = 8286) and without (n = 4654) CKD, were followed for 55,206 person-years. Higher rates of HRU were observed for gout patients with CKD than without. Total annual hospital admissions for patients with gout and CKD were at least 3 times higher for adults < 55 (mean = 0.51 vs 0.13) and approximately 1.5 times higher for adults 55+ (mean = 0.46 vs 0.29) without CKD. Healthcare utilization rates from year 1 to year 5 remained similar for gout patients < 55 years irrespective of CKD status, however varied according to healthcare utilization by CKD status for gout patients 55+ years. The 5-year all-cause mortality was higher among those with CKD compared to those without CKD for both age groups (HR< 55 years = 1.65; 95% CI 1.01–2.71; HR55+ years = 1.50; 95% CI 1.37–1.65). The current study suggests important differences exist in patient characteristics and outcomes among patients with gout and CKD. Healthcare utilization differed between sub-populations, age and comorbidities, over the study period and the 5-year mortality risk was higher for gout patients with CKD, regardless of age. Future work should explore factors associated with these outcomes and barriers to gout control in order to enhance patient management among this high-risk subgroup.

  • Intensive management for moderate rheumatoid arthritis: a qualitative study of patients’ and practitioners’ views
    BMC Rheumatol. (IF 0) Pub Date : 2019-03-28
    Louise Prothero; Jackie Sturt; Savia de Souza; Heidi Lempp

    The TITRATE trial seeks to test whether intensive management is valuable in achieving disease remission in moderately active rheumatoid arthritis. Intensive management is a complex intervention consisting of: 1) 12 x monthly appointments, 2) tailored ‘treatment support’ based on motivational interviewing techniques, 3) optimised medication (including the opportunity for biologics), 4) provision of a Patient Handbook, and 5) shared treatment planning. This study aims to understand: a) patients’ and practitioners’ views on the feasibility and acceptability of intensive management, and b) patients’ and practitioners’ experience of receiving/providing intensive management. A qualitative study, nested within a randomised controlled trial. Participants were patients (n = 15) in the intensive management arm of the trial and rheumatology practitioners (n = 16) providing the intensive management intervention, from 18/42 clinics across England. Data were collected via semi-structured interviews and analysed using thematic analysis and iterative categorization. Monthly appointments were largely acceptable to both groups who cited several treatment benefits (e.g. regular review of medication, practitioners built close relationships with patients). Practitioners were ‘fairly confident’ using the motivational interviewing techniques. Learning to pace was the most commonly reported self-management technique that patients and healthcare professionals worked on together, followed by gaining control over pain and fatigue. Practitioners liked having the option to offer biologics to patients with moderate RA. Most patients found the optimised medication (following monthly joint assessment) helpful and side-effects experienced were resolved. Variation existed in the extent to which patients engaged with the Patient Handbook and shared treatment planning, with those who did engage doing so in the early stages. Feedback from patient participants about the intensive management intervention was positive. They found increased medication helpful. Continuity of care with the same healthcare professional at regular intensive management sessions, and the treatment support provided, were highly rated. Feedback from practitioners indicated that intensive management training is feasible. Evidence from the interviews showed that some practitioners applied motivational interviewing techniques during standard care appointments and they would like the opportunity to address lifestyle issues with patients.

  • The utility of ESR, CRP and platelets in the diagnosis of GCA
    BMC Rheumatol. (IF 0) Pub Date : 2019-04-10
    Fiona Li Ying Chan; Susan Lester; Samuel Lawrence Whittle; Catherine Louise Hill

    To compare the utility of ESR, CRP and platelets for the diagnosis of GCA. A clinical diagnosis of GCA was determined by case-note review of 270 individuals (68% female, mean age 72 years) referred to a central pathology service for a temporal artery biopsy between 2011 and 2014. The highest levels of ESR, CRP and platelets (within 2 weeks of diagnosis) were documented. Evaluation of ESR, CRP and platelets for the diagnosis of GCA were compared using Receiver Operating Characteristic Area Under the Curve (ROC-AUC), and sensitivity/specificity at optimum cut-off values. GCA was clinically diagnosed in 139 (67%) patients, with 81 TAB positive. The AUC estimates for ESR, CRP and platelets were comparable (0.65 vs 0.72 vs 0.72, p = 0.08). The estimated optimal cut-off levels were confirmed at 50 mm/hour for ESR, and determined as 20 mg/L for CRP and 300 × 109/L for platelets. Sensitivity estimates for these three tests were comparable (p = 0.45) and ranged between 66% for ESR and 71% for platelets. Specificity estimates were also comparable (p = 0.11) and ranged between 57% for ESR and 68% for CRP. There was only moderate agreement between the three positive tests (agreement 67%, kappa: 0.34), and when considered collectively, CRP and platelet positive tests were independent predictors of GCA (p < 0.001), but the ESR was not (p = 0.76). ESR, CRP and platelets are moderate, equivalent diagnostic tests for GCA, but may yield disparate results in individual patients. A combination of CRP and platelet tests may provide the best diagnostic utility for GCA.

  • Effects of tofacitinib on the clinical features of periodontitis in patients with rheumatoid arthritis: two case reports
    BMC Rheumatol. (IF 0) Pub Date : 2019-04-19
    Tetsuo Kobayashi; Satoshi Ito; Akira Murasawa; Hajime Ishikawa; Hiromasa Yoshie

    The pathobiology of rheumatoid arthritis (RA) is similar to that of periodontitis in that proinflammatory cytokines play an important pathologic role. There is evidence to suggest that inhibitors of tumor necrosis factor (TNF) and interleukin-6 (IL-6) receptor for the treatment of RA ameliorated periodontal inflammation. However, no study has evaluated the effect of tofacitinib, an oral Janus kinase inhibitor for the treatment of RA, on periodontitis. The present report cases are 51- and 43-year-old non-smoking women with RA who demonstrated localized moderate chronic periodontitis. Both cases showed improvement in the periodontal inflammatory condition after 3 months of tofacitinib therapy, although the teeth count and supragingival bacterial plaque level were relatively unchanged. Improvements were also observed in the serum levels of IL-6 in both cases as well as in the serum levels of TNF-α and anti-cyclic citrullinated peptide immunoglobulin G in one case and of rheumatoid factor and matrix metalloproteinase-3 in the other case. Patients who received tofacitinib exhibited an inconsistent clinical response, likely due to the low disease activity of RA at the start of the administration. These are the first reported cases in which tofacitinib may have a beneficial effect on periodontitis. However, more research is required to understand the relationship between periodontitis and tofacitinib therapy.

  • Efficacy of subcutaneous tocilizumab in patients with rheumatoid arthritis and systemic sclerosis overlap syndrome: a report of two cases and review of the literature
    BMC Rheumatol. (IF 0) Pub Date : 2019-04-24
    Hiroki Wakabayashi; Hitoshi Kino; Makoto Kondo; Keiichi Yamanaka; Masahiro Hasegawa; Akihiro Sudo

    The details of two rheumatoid arthritis (RA) patients with systemic sclerosis (SSc) who were administered tocilizumab, an anti-interleukin-6 receptor antibody, are reported, along with a review of the literature. Two RA patients with SSc with inadequate responses to disease-modifying antirheumatic drugs (DMARDs) were given tocilizumab 162 mg every 2 weeks for 18 months. RA disease activity was evaluated by the 28-joint disease activity score with erythrocyte sedimentation rate (DAS28-ESR) and the clinical disease activity index (CDAI). The skin condition of SSc was evaluated by pinching the skin according to the modified Rodnan total skin thickness score (mRSS). Softening of the skin and improvements of arthritis and the patient global assessment were observed during tocilizumab treatment, with reduction of not only RA disease activity, but also of the mRSS. Tocilizumab may be effective in patients with RA and SSc overlap syndrome for which conventional treatment is inadequate. Further research is needed because this report included only two patients.

  • Cost-effectiveness of different treat-to-target strategies in rheumatoid arthritis: results from the DREAM registry
    BMC Rheumatol. (IF 0) Pub Date : 2019-04-29
    Celine J. van de Laar; Martijn A. H. Oude Voshaar; Harald E. Vonkeman

    Adjusting medication of patients with rheumatoid arthritis (RA) until predefined disease activity targets are met, i.e. Treat-to-Target (T2T), is the currently recommended treatment approach. However, not much is known about long-term cost-effectiveness of different T2T strategies. We model the 5-year costs and effects of a step-up approach (MTX mono - > MTX + csDMARD combination - > Adalimumab - > second anti-TNF) and an initial combination therapy approach (MTX + csDMARD - > MTX + csDMARD higher dose - > anti-TNFs) from the healthcare and societal perspectives, by adapting a previously validated Markov model. We constructed a Markov model in which 3-monthly transitions between DAS28-defined health states of remission (≤2.6), low (2.6 < DAS28 ≤ 3.2), moderate (3.2 < DAS28 ≤ 5.1), and high disease activity (DAS28 > 5.1) were simulated. Modelled patients proceeded to subsequent treatments in case of non-remission at each (3-month) cycle start. In case of remission for two consecutive cycles medication was tapered, until medication-free remission was achieved. Transition probabilities for individual treatment steps were estimated using data of Dutch Rheumatology Monitoring registry Remission Induction Cohort I (step-up) and II (initial combination). Expected costs, utility, and ICER after 5 years were compared between the two strategies. To account for parameter uncertainty, probabilistic sensitivity analysis was employed through Gamma, Normal, and Dirichlet distributions. All utilities, costs, and transition probabilities were replaced by fitted distributions. Over a 5-year timespan, initial combination therapy was less costly and more effective than step-up therapy. Initial combination therapy accrued €16,226.3 and 3.552 QALY vs €20,183.3 and 3.517 QALYs for step-up therapy. This resulted in a negative ICER, indicating that initial combination therapy was both less costly and more effective in terms of utility gained. This can be explained by higher (±5%) remission percentages in initial combination strategy at all time points. More patients in remission generates less healthcare and productivity loss costs and higher utility. Additionally, higher remission percentages caused less bDMARD use in the initial combination strategy, lowering overall costs. Initial combination therapy was found favourable over step-up therapy in the treatment of Rheumatoid Arthritis, when considering cost-effectiveness. Initial combination therapy resulted in more utility at a lower cost over 5 years.

  • Management of Inflammatory Arthritis in pregnancy: a National Cross-Sectional Survey of Canadian rheumatologists
    BMC Rheumatol. (IF 0) Pub Date : 2019-05-17
    Mary A. De Vera; Corisande Baldwin; Nicole W. Tsao; Alyssa Howren; Glen S. Hazlewood; Nevena Rebić; Stephanie Ensworth

    With improved therapies and management, more women with inflammatory arthritides (IA) are considering pregnancy. Our objective was to survey rheumatologists across Canada about their IA management in pregnancy to identify practice patterns and knowledge gaps. We administered an online survey with questions regarding medications for IA treatment including conventional synthetic disease modifying antirheumatic drugs (csDMARDs) and biologics/small molecules in planned and unplanned pregnancies. Email invitations were sent to members of the Canadian Rheumatology Association. We calculated responses frequencies and a priori set a cut-off of ≥75% to define consensus. Ninety rheumatologists participated in the survey (20% participation rate); 57% have been practicing for > 10 years, 32% for ≤10 years, and 11% in training. There was consensus on discontinuation of 4 csDMARDs – cyclophosphamide (100%), leflunomide (98%), methotrexate (96%), and mycophenolate mofetil (89%) – in planned pregnancies but varied responses on when to discontinue them or what to do in unplanned pregnancies. Respondents agreed that 3 csDMARDs – azathioprine (84%), hydroxychloroquine (95%), and sulfasalazine (77%) – were safe to continue in planned and unplanned pregnancies. There was consensus with use of 4 biologics – adalimumab (81%), certolizumab (80%), etanercept (83%), and infliximab (76%) – in planned pregnancies but uncertainty on when they should be discontinued and their use in unplanned pregnancies. This national survey shows consensus among rheumatologists on the use of some csDMARDs and biologics/small molecules in IA patients planning pregnancy but varied knowledge on when to discontinue and what to do in unplanned pregnancies.

  • AxSpA patients who also meet criteria for fibromyalgia: identifying distinct patient clusters using data from a UK national register (BSRBR-AS)
    BMC Rheumatol. (IF 0) Pub Date : 2019-05-20
    Gary J. Macfarlane; Ejaz Pathan; Stefan Siebert; Jonathan Packham; Karl Gaffney; Ernest Choy; Raj Sengupta; Fabiola Atzeni; Kathryn R. Martin; Gareth T. Jones; Linda E. Dean

    Around 1 in 8 patients with axial spondyloarthritis (axSpA) also meet criteria for fibromyalgia and such patients have considerable unmet need. Identifying effective therapy is important but to what extent fibromyalgia-like symptoms relate to axSpA disease severity has not been established. The aim of the current analysis was to determine whether distinct clusters of axSpA patients exist and if so to determine a) whether they differ in terms of prevalence of fibromyalgia and b) the features of patients in clusters with high prevalence. The British Society for Rheumatology Biologics Register (BSRBR-AS) recruited axSpA patients from 83 centres 2012–2017. Clinical data, and information from patients was collected (including research criteria for fibromyalgia). Cluster analysis was undertaken using split samples for development and validation both in the whole population and the sub-group which met fibromyalgia criteria. One thousand three hundred thirty-eight participants were included of whom 23% met research criteria for fibromyalgia. Four clusters were identified. Two exhibited very high disease activity, one which was primarily axial (n = 347) and a smaller cluster (n = 32) with axial and peripheral disease, and in both groups more than half of members met criteria for fibromyalgia. The remaining two clusters (n = 437, n = 462) had overall less severe disease however the one which showed greater disease activity and poorer quality of life had a higher proportion meeting fibromyalgia criteria (16% v. 4%). Within those meeting fibromyalgia criteria there were three clusters. The two main groups were defined by level of symptom severity with a smaller third cluster noted to have high average swollen and tender joint counts and high levels of comorbidity. The major feature defining clusters with a high proportion of persons meeting criteria for fibromyalgia is high axSpA disease activity although clusters with features of fibromyalgia in the absence of high disease activity also show moderately high prevalence. Management may be most successful with pharmacologic therapy to target inflammation but enhanced by the concurrent use of non-pharmacologic therapy in such patients.

  • Quality and continuity of information between primary care physicians and rheumatologists
    BMC Rheumatol. (IF 0) Pub Date : 2019-05-24
    Jenna Wong; Karen Tu; Sasha Bernatsky; Liisa Jaakkimainen; J. Carter Thorne; Vandana Ahluwalia; J. Michael Paterson; Jessica Widdifield

    Good communication is central to a high-quality consultation process. We assessed the quality of referral information from primary care physicians (PCPs) to rheumatologists and the quality and timeliness of consultation letters from rheumatologists back to PCPs. We sampled referral letters between 2000 and 2013 from 168 PCPs and performed a retrospective chart review of 2430 patients referred to 146 rheumatologists. We assessed the completeness and timeliness of referral and consultation letters. Osteoarthritis (n = 787, 32%) and systemic inflammatory rheumatic diseases (n = 745, 31%) comprised the top reasons for referral. Only 55% of referral letters summarized the patients’ medical history. Referral letters provided some details of diagnostic tests (51% labs, 34% imaging) but there was underreporting of this information on referral letters. Almost all referral letters (92%) contained details of at least one patient symptom, with the most common complaint being joint pain (54%). Only half of all referral letters provided symptom duration. The PCP only stressed an urgent consultation among 211 patients (9%). Overall, 69% of consultation letters were returned to PCPs within 30 days of consultation visit. We found that basic items necessary for appropriate triage, including a description of symptoms or other relevant history and results of investigations were often lacking in referral letters. The delay of receipt of consultation letters may further represent a lost opportunity for coordination and continuity of care, and may affect the quality of care patients receive.

  • Fatty corner lesions in T1-weighted magnetic resonance imaging as an alternative to sacroiliitis for diagnosis of axial spondyloarthritis
    BMC Rheumatol. (IF 0) Pub Date : 2019-05-30
    Ho Yin Chung; Rachel Sze Wan Yiu; Shirley Chiu Wai Chan; Kam Ho Lee; Chak Sing Lau

    A fatty corner lesion (FCL) is a well-demarcated fat infiltration in the corner of a vertebral body on T1 magnetic resonance imaging (MRI) sequence. It has been reported to be useful in the diagnosis of axial spondyloarthritis (axSpA). Our objective is to systematically evaluate the diagnostic accuracy of FCLs in tertiary centre patients with chronic back pain. Two hundred and thirty eight axSpA patients and 62 non-axSpA patients with back pain were recruited from five rheumatology centres. Clinical, biochemical, and radiological parameters were collected and all patients underwent a MRI of the spine and sacroiliac (SI) joints. FCLs in vertebral bodies from C4 to L5 were scored. The number and location of FCLs were clustered together to determine an optimal combination for diagnosis. Results were compared with expert diagnosis as the “gold standard”. FCLs of the anterior whole spine (AUC 0.62; p = 0.003) and anterior thoracic spine (AUC 0.64; p = 0.001) had diagnostic significance. Incorporating at least 5 whole spine FCLs into the imaging criteria of the Assessment of SpondyloArthritis international Society (ASAS) criteria for axSpA yielded a sensitivity of 91.6% and specificity of 91.9%. Similarly, applying at least 3 anterior thoracic FCLs to the imaging criteria of the ASAS axial SpA criteria yielded a sensitivity of 92.0% and specificity of 93.5%. FCLs could be used to diagnose axial SpA. The presence of at least 3 anterior thoracic FCLs in T1-weighted MRI spine suggests a diagnosis of axial SpA without additional MRI of the SI joints. The cohort has been registered in the clinical trial registry of the University of Hong Kong ( HKUCTR-2087 ).

  • Predictors of biologic-free disease control in patients with rheumatoid arthritis after stopping tumor necrosis factor inhibitor treatment
    BMC Rheumatol. (IF 0) Pub Date : 2019-06-13
    Marjan Ghiti Moghadam; Femke B. G. Lamers-Karnebeek; Harald E. Vonkeman; Peter M. ten Klooster; Janneke Tekstra; Barbara van Schaeybroeck; Ruth Klaasen; Marieke van Onna; Hein J. Bernelot Moens; Henk Visser; Annemarie M. Schilder; Marc R. Kok; Robert B. M. Landewé; Piet L. C. M. van Riel; Mart A. F. J. van de Laar; Tim L. Jansen

    The aim of this study was to identify predictors of prolonged disease control after discontinuation of tumor necrosis factor inhibitor (TNFi) treatment in patients with rheumatoid arthritis (RA). Post-hoc analysis of 439 RA patients (67.3% rheumatoid factor positive) with longstanding RA in remission or with stable low disease activity, randomized to stopping TNFi treatment in the multicenter POET trial. Prolonged acceptable disease control was defined as not restarting TNFi treatment within 12 months after stopping. Baseline demographic and disease-related variables were included in univariate and multivariate logistic regression analysis for identifying predictors of relapse. One year after baseline, 220 patients (50.1%) had not restarted TNFi treatment. Use of an anti-TNF monoclonal antibody (versus a receptor antagonist, OR = 2.41; 95% CI: 1.58–3.67), ≤10 yrs. disease duration (OR = 2.15; 95% CI: 1.42–3.26) and low or moderate multi-biomarker disease activity (MBDA) scores (OR = 2.00; 95% CI: 1.10–3.64) at baseline were independently predictive of successful TNFi discontinuation (area under the receiver operating characteristic curve = 0.66; 95% CI: 0.61–0.71). Results were similar when using no physician-reported flare as the criterion. TNFi-free survival was significantly different for patient groups based on the number of predictors present, ranging from 21.4% of patients with no predictor present to 66.7% of patients with all three predictors present. Patients using an anti-TNF monoclonal antibody, with shorter disease duration and low or moderate baseline MBDA score are most likely to achieve prolonged disease control after TNFi discontinuation. Netherlands Trial Register NTR3112 , 21 October 2011.

  • “Living a normal life”: a qualitative study of patients’ views of medication withdrawal in rheumatoid arthritis
    BMC Rheumatol. (IF 0) Pub Date : 2019-06-13
    Kenneth F. Baker; John D. Isaacs; Ben Thompson

    Withdrawal of disease-modifying anti-rheumatic drugs (DMARDs) once disease remission is achieved is endorsed by current international rheumatoid arthritis (RA) management guidelines. However, very little data exists concerning patients’ views of this practice. In this qualitative study, we aimed to explore patients’ perspectives on DMARD withdrawal in the setting of established RA. In this qualitative interview study, patients with stable established RA were recruited from rheumatology outpatient clinics at a large UK teaching hospital. The perceived advantages and disadvantages of DMARDs and views on DMARD withdrawal were explored in semi-structured interviews. Interview transcripts were analysed using standard qualitative techniques to construct an analytical framework. Thirteen participants (8 female, median [IQR] age 65 [61–73]) expressed their views of DMARD treatment in the context of their “normal lives”. For some patients, disadvantages such as medication side-effects and the inconvenience of safety monitoring were sufficient hindrances to their lifestyle to justify DMARD withdrawal. However, patients who were vulnerable to loss of physical function, or who had prior experience of severe rheumatoid arthritis, expressed a strong preference against DMARD withdrawal, viewing the potential for increased pain and future disability as unacceptable risks. Patients view DMARD withdrawal in the context of either restoring or threatening their “normal lives”. In this model, social and personal factors play a crucial role in influencing patients’ opinions of DMARD therapy beyond a simple consideration of medication side-effects alone. A formulaic approach to DMARD withdrawal determined and imposed by clinicians would not be successful. Instead, the discussion of DMARD withdrawal should take place with the identification of patients’ priorities and in the context of their personal disease experiences. clinicaltrials.gov (NCT02064400), retrospectively registered 17 February 2014.

  • Development and psychometric properties of a self-care behaviors scale (SCBS) among patients with rheumatoid arthritis
    BMC Rheumatol. (IF 0) Pub Date : 2019-06-18
    Haidar Nadrian; Yasna Hosseini Niaz; Zahra Basiri; Ahmad Tahamoli Roudsari

    The role of self-care behaviors in promoting physical function, pain management, health status and quality of life among patients with Rheumatoid Arthritis (RA) is well documented. However, there is no valid and reliable instrument in the literature to assess such behaviors among the patients. In the present study, we aimed to develop and assess the psychometric properties of a Self-care Behaviors Scale (SCBS) among patients with RA. In 2017, applying a cross-sectional design, we recruited a convenient sample of 436 RA patients in Hamadan, Iran, to participate in the study. We developed the initial scale, including 30 items, after literature review, and having recommendations from an expert panel. Face, content, construct and convergent validity, as well as reliability of the scale were investigated. In Exploratory Factor Analysis, the optimal solution comprising 25 items and 7 factors was emerged, which explained 62.5% of all variances between the items. In Confirmatory Factor Analysis, the measurement model fit the data well, and all subscales were significant within an acceptable range (χ2 [233] = 428.654, p < 0.0001, comparative fit index = 0.942, normed fit index =0.907, Tucker-Lewis index =0.916, and root mean square error of approximation = 0.043[(0.037–0.05]). The Self-care Behaviors Scale was found with appropriate validity, reliability, functionality and simplicity. To our knowledge, this scale is the only valid and reliable RA specific self-care behavior scale in the literature. Healthcare providers and health practitioners may apply the English version of this suitable instrument to find more valid and reliable data on RA self-care behaviors during primary assessments of the behaviors in educational interventions for the patients.

  • Stress levels predict substantial improvement in pain intensity after 10 to 12 years in women with fibromyalgia and chronic widespread pain: a cohort study
    BMC Rheumatol. (IF 0) Pub Date : 2019-06-24
    Anna Bergenheim; Sofia Juhlin; Lena Nordeman; Monica Joelsson; Kaisa Mannerkorpi

    Previous studies of prognosis for women with Fibromyalgia (FM) or chronic widespread pain (CWP) show contradictory results. However, some women appear to improve in pain and other core symptoms over time. There is limited knowledge about predictors of substantial improvement in pain intensity over a longer period of time. The primary objective of this study was to investigate the natural course of pain intensity and distribution of pain over 10 to 12 years in a cohort of 166 women with FM or CWP. Secondarily we wanted to investigate predictors of substantial improvement (≥50%) in pain intensity after 10 to 12 years. The study is a longitudinal prospective cohort study. 166 women with FM or CWP were followed up after 10 to 12 years. 126 women (76%) participated in the follow-up and completed a battery of questionnaires concerning pain intensity, pain distribution and other physical and mental aspects of health. Differences in symptoms within the cohort over 10 to 12 years and predictors of substantial improvement (≥50%) in pain intensity were calculated. Pain had improved at the 10 to 12 year follow-up (p < 0.001) with a mean change of − 9.2 mm (SD 23.3, 95% CI: − 13.3; − 5.0) for pain intensity and − 2.0 sites (SD 4.2, 95% CI: − 2.7; − 1.2) for pain distribution. Nine percent of the 126 women showed an individual moderate improvement in pain intensity while 16% showed a substantial improvement at the follow-up as compared to baseline. Lower symptoms of stress and higher pain intensity at baseline predicted higher probability of reporting at least 50% less pain intensity after 10 to 12 years as compared to baseline. A majority of women with FM and CWP appear to have a positive course of pain over time, which should be communicated to these patients in health care. Reducing stress levels might contribute to better chances of improvement over time. Clinicaltrials.gov NCT02872129 , registered 06/30/2016.

  • The prevalence and types of discordance between physician perception and objective data from standardized measures of rheumatoid arthritis disease activity in real-world clinical practice in the US
    BMC Rheumatol. (IF 0) Pub Date : 2019-07-04
    Wenhui Wei; Emma Sullivan; Stuart Blackburn; Chieh-I Chen; James Piercy; Jeffrey R. Curtis

    Heterogeneity in assessments of rheumatoid arthritis (RA) disease remission, based on physician judgment and patient self-reports versus standardized measures, have previously been reported. This study explored the prevalence and types of discordance between physician perception versus objective data of RA disease activity in real-world clinical practice in the US. Data were from the Adelphi RA Disease Specific Programme (DSP; January to March 2014), a cross-sectional survey of US rheumatologists and their patients. RA remission based on physician judgment versus Disease Activity Score in 28 joints (3)-erythrocyte sedimentation rate (DAS28(3)-ESR) and Clinical Disease Activity Index (CDAI) scores were compared using descriptive analyses; patient and physician factors associated with discordance were identified using bivariate and multivariate analyses. Of 101 rheumatologists participating (completing patient-record forms for 843 patients), 56.4% based assessment of remission on clinical judgment alone. Of 531 patients eligible for the discordance analysis, 49.7% were in remission based on rheumatologists’ evaluation, and 30.7% were eligible based on DAS28(3)-ESR. Compared with DAS28(3)-ESR criteria, 25.8% of patients’ disease remission was negatively discordant (overestimated remission) based on clinical perception. These patients were mostly administered biologic disease-modifying antirheumatic drugs and were without a treat-to-target strategy followed by their rheumatologist (P < 0.05). These patients were also more likely to have experienced a higher level of pain as well as increased joint inflammation and damage (e.g. destruction of cartilage, thinning of bone, and/or synovium inflammation) compared with concordant patients (P < 0.005). Conversely, 6.8% of rheumatologists were positively discordant (under estimated remission) versus the DAS28(3)-ESR. Sensitivity analysis indicated different levels of discordance using CDAI, with 35.6% negative discordance and 1.3% positive discordance of rheumatologist-assessed disease remission compared with objective data. There is discordance between RA remission as assessed by rheumatologist perception versus standardized measures among those in the US DSP sample. Our study identified the factors associated with the discordance which may inform strategies to enhance assessments of RA disease remission.

  • The challenges of gout flare reporting: mapping flares during a randomized controlled trial
    BMC Rheumatol. (IF 0) Pub Date : 2019-07-09
    Novell Teoh; Gregory D. Gamble; Anne Horne; William J. Taylor; Kate Palmano; Nicola Dalbeth

    Methods of gout flare reporting in research settings are inconsistent and poorly defined. The aim of this study was to describe patterns of gout flare and assess the concurrent validity of different methods of flare reporting in a gout clinical trial. Daily flare diary entries including self-report of flare and pain scale from a randomised controlled trial of 120 patients with gout were analysed. Detailed pain-by-time plots for each participant were inspected and analysed for different methods of flare reporting for both self-report and the classification tree (CART)-defined flare developed by Gaffo in 2012. Concurrent validity for different methods of flare reporting were analysed. Although the single gout flare had a ‘typical’ average pattern (peak on day 1 and resolution over 14 days), individual pain-by-time plots showed wide variation in pain intensity, duration and frequency of flares. Over the four-month study period, there were 84/120 (70%) participants who experienced at least one self-reported flare that was not a ‘typical’ flare. The time to first self-reported flare correlated poorly with other measures of gout activity and other methods of flare reporting. The number of days with flare (either self-reported or Gaffo-defined) and the area under the pain-by-time curve correlated most strongly with other measures of disease severity. There is wide variation in the patterns of flare over time in individuals with gout, leading to challenges for flare reporting in clinical trials. Time-dependent reporting strategies such as number of days with flare or area under the pain-by-time curve correlate well with other measures of gout disease severity and may provide a more accurate measure of flare burden. Clinical trial number: ACTRN12609000479202 , registered 17/06/2009.

  • Incidence and prevalence of rheumatoid arthritis in Saskatchewan, Canada: 2001–2014
    BMC Rheumatol. (IF 0) Pub Date : 2019-07-18
    Bindu Nair; Regina Taylor-Gjevre; Liying Wu; Shan Jin; Jacqueline M. Quail

    Rheumatoid arthritis (RA) is a chronic inflammatory and destructive arthritis. Understanding the incidence and prevalence of RA within the province facilitates appropriate health care resource planning. To estimate the incidence/prevalence of RA over time for the overall provincial population, for specific age range categories, and for gender. Saskatchewan Provincial Administrative Health Databases (2001–2014) were utilized as data sources. Two RA case-definitions were employed: 1) > three physician billing diagnoses, at least one of which was submitted by a specialist (rheumatologist, general internist or orthopedic surgeon) within 2 years; 2) > one hospitalization diagnosis (ICD-9-CM code-714, and ICD-10-CA code-M05). Data from these definitions were combined to identify incident and prevalent RA cases. Using this data, annual incidence and prevalence rates were calculated for the provincial population, specified age range categories and gender categories. The number of RA cases meeting the case definition increased from 3731 to 6223 over the study period. The incidence of RA disease demonstrated variation within the study period with age and sex adjusted incidence ranging from 33.6 (95% CI 29.9–37.6) per 100,000 to 73.1 (95% CI 67.6–79.0) per 100,000. The prevalence of RA increased over time from 482 (95% CI 466.7–497.7) per 100,000 in 2001–2002 to 683.4 (95% CI 666.6–700.6) per 100,000 in 2014–2015. Both incidence and prevalence rates rose with increasing age. Women were found to have higher incidence and prevalence rates compared to men. In Saskatchewan, the overall prevalence of RA is rising while there has been variability in the incidence.

  • Administrative database as a source for assessment of systemic lupus erythematosus prevalence: Estonian experience
    BMC Rheumatol. (IF 0) Pub Date : 2019-07-25
    Kati Otsa; Sandra Talli; Pille Harding; Eevi Parsik; Marge Esko; Anti Teepere; Marika Tammaru

    Administrative database research is widely applied in the field of epidemiology. However, the results of the studies depend on the type of database used and the algorithms applied for case ascertainment. The optimal methodology for identifying patients with rheumatic diseases from administrative databases is yet not known. Our aim was to describe an administrative database as a source for estimation of epidemiological characteristics on an example of systemic lupus erythematosus (SLE, ICD-10 code M32) prevalence assessment in the database of the Estonian Health Insurance Fund (EHIF). Code M32 billing episodes were extracted from the EHIF database 2006–2010. For all cases where M32 was assigned by a rheumatologist less than four times during the study period, diagnosis verification process using health care providers’ (HCP) databases was applied. For M32 cases assigned by a rheumatologist four times or more, diagnoses were verified for a randomly selected sample. From 677 persons with code M32 assigned in EHIF database, 404 were demonstrated having “true SLE”. The code M32 positive predictive value (PPV) for the whole EHIF database was 60%; PPV varies remarkably by specialty of a physician and repetition of the code assignment. The false positive M32 codes were predominantly initial diagnoses which were not confirmed afterwards; in many cases, a rheumatic condition other than SLE was later diagnosed. False positive codes due to tentative diagnoses may be characteristic for conditions with a complicated diagnosis process like SLE and need to be taken into account when performing administrative database research.

  • Retinal vasculitis with Chronic Recurrent Multifocal Osteomyelitis: a case report and review of the literature
    BMC Rheumatol. (IF 0) Pub Date : 2019-08-01
    Victoria K. Shanmugam; Marc Phillpotts; Timothy Brady; Monica Dalal; Shawn Haji-Momenian; Esma Akin; Kavita Nataranjan; Sean McNish; Donald S. Karcher

    Concurrent presentation of retinal vasculitis with mixed sclerotic and lytic bone lesions is rare. We present the case of a 37-year old woman with a several year history of episodic sternoclavicular pain who presented for rheumatologic evaluation due to a recent diagnosis of retinal vasculitis. We review the differential diagnosis of retinal vasculitis, along with the differential diagnosis of mixed sclerotic and lytic bone lesions. Ultimately, bone marrow biopsy confirmed diagnosis of chronic recurrent multifocal osteomyelitis (CRMO). Concurrent presentation of CRMO with retinal vasculitis is extremely rare but important to recognize. The patient demonstrated clinical response to prednisone and tumor necrosis factor-alpha inhibition (TNF-i). This case reports and unusual presentation of CRMO spectrum disease involving the sternum and sternoclavicular joint with concurrent retinal vasculitis.

  • Biomarkers of cardiovascular risk across phenotypes of osteoarthritis
    BMC Rheumatol. (IF 0) Pub Date : 2019-08-08
    S. A. Provan; S. Rollefstad; E. Ikdahl; A. Mathiessen; I. J. Berg; I. Eeg; I. B. Wilkinson; C. M. McEniery; T. K. Kvien; H. B. Hammer; N. Østerås; I. K. Haugen; A. G. Semb

    The objective of this study was to explore the associations between ultrasonographic and radiographic joint scores and levels of arterial CVD risk markers in patients with osteoarthritis (OA). Secondly, to compare the levels of arterial CVD risk markers between OA phenotypes and controls. The “Musculoskeletal pain in Ullensaker” Study (MUST) invited residents of Ullensaker municipality with self-reported OA to a medical examination. OA was defined according to the American College of Rheumatology (ACR) criteria and phenotyped based on joint distribution. Joints of the hands, hips and knees were examined by ultrasonography and conventional radiography, and scored for osteosteophytes. Hands were also scored for inflammation by grey scale (GS) synovitis and power Doppler (PD) signal. Control populations were a cohort of inhabitants of Oslo (OCP), and for external validation, a UK community-based register (UKPC). Pulse pressure augmentation index (AIx) and pulse wave velocity (PWV) were measured using the Sphygmocor apparatus (Atcor®). Ankel-brachial index (ABI) was estimated in a subset of patients. In separate adjusted regression models we explored the associations between ultrasonography and radiograph joint scores and AIx, PWV and ABI. CVD risk markers were also compared between phenotypes of OA and controls in adjusted analyses. Three hundred and sixty six persons with OA were included (mean age (range); 63.0 (42.0–75.0)), (females (%); 264 (72)). Of these, 155 (42.3%) had isolated hand OA, 111 (30.3%) had isolated lower limb OA and 100 (27.3%) had generalized OA. 108 persons were included in the OCP and 963 persons in the UKPC; (mean age (range); OCP: 57.2 (40.4–70.4), UKPC: 63.9 (40.0–75.0), females (%); OCP: 47 (43.5), UKPC: 543 (56.4%). Hand osteophytes were associated with AIx while GS and PD scores were not related to CVD risk markers. All OA phenotypes had higher levels of AIx compared to OCP in adjusted analyses. External validation against UKPC confirmed these findings. Hand osteophytes might be related to higher risk of CVD. People with OA had higher augmented central pressure compared to controls. Words 330.

  • Health-related quality of life in patients with rheumatoid arthritis
    BMC Rheumatol. (IF 0) Pub Date : 2019-08-14
    Wanruchada Katchamart; Pongthorn Narongroeknawin; Wanwisa Chanapai; Phakhamon Thaweeratthakul

    Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects joints with some extraarticular involvement. If inappropriately treated, it usually results in persistent joint pain, irreversible deformities, and functional disability, leading to poor quality of life. Our objective was to evaluate health-related quality of life (HRQoL) and related factors in patients with RA. Four hundred sixty-four patients from the Rheumatoid Arthritis registries of Siriraj and Phramongkutklao teaching hospitals were enrolled. Sociodemographic, clinical and laboratory data related to disease activity, and functional status were collected. HRQoL was assessed using the Thai version of EuroQol five dimensional questionnaire (EQ-5D) and EQ global health visual analogue scale (EQ VAS). Univariate and multivariate analyses were employed to identify factors related to HRQoL. Eighty-five percent were female with a mean age ± SD of 59.15 ± 11.43 years and a mean disease duration ± SD of 11.53 ± 8.3 years. The mean educational level ± SD was 9.42 ± 5.21 years. Almost half were unemployed or retired (47%). They had moderate disease activity (mean cumulative DAS28 ± SD, 3.5 ± 0.8) and mild functional impairment (mean HAQ ± SD, 0.70 ± 0.68). The mean EQ-5D ± SD (0–1) was 0.87 ± 0.13 and mean EQ VAS ± SD (0–10) was 7.94 ± 1.7. Based on the EQ-5D domain, 49% reported that they had no problem with mobility, 83% had no difficulties with self-care, 65% had no difficulties with usual activity, 30% had no pain or discomfort, and 61% had no depression or anxiety. The relationship between problems of each dimension in EQ-5D significantly increased according to severity of RA assessed by the Disease Activity Score (DAS) 28 and Health Assessment Questionnaire (HAQ) (p < 0.01). In multivariate analyses, high cumulative disease activity, functional disability, depression, and anxiety were negatively associated with EQ-5D (adjusted R2 0.38, p < 0.001) and EQ VAS (adjusted R 2 0.19, p < 0.001). Disease severity and psychological disturbance have a negative impact on quality of life in patients with RA. These factors should be considered in management of RA patients to improve the standard of care.

  • Abstracts of scientific contributions to GCOM 2019
    BMC Rheumatol. (IF 0) Pub Date : 2019-08-19

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  • Publisher Correction to: BMC Rheumatology, volume 3
    BMC Rheumatol. (IF 0) Pub Date : 2019-08-20

    An error occurred during the publication of a number of articles in BMC Rheumatology. Several articles were published in volume 3 with a duplicate citation number.

  • Immunoglobulin abnormalities are frequent in patients with lupus nephritis
    BMC Rheumatol. (IF 0) Pub Date : 2019-08-21
    M. J. Cuadrado; I. Calatayud; M. Urquizu-Padilla; S. Wijetilleka; S. Kiani-Alikhan; M. Y. Karim

    Hypogammaglobulinemia is a complication of B-cell targeting therapies (BCTT), used in vasculitis, rheumatoid arthritis and systemic lupus erythematosus (SLE). Since autoimmune diseases are associated with underlying and induced immune abnormalities, several societies recommend assessing immune function before and during rituximab treatment. In SLE, polyclonal hypergammaglobulinemia is the typical alteration of gammaglobulins, though hypogammaglobulinemia has also been reported. This is a cross-sectional study describing immunoglobulin levels measured as part of routine care in patients with lupus nephritis, a group with multiple factors contributing to immunoglobulin abnormalities, including immune dysregulation, immunosuppression and nephrotic syndrome. Polyclonal hypergammaglobulinemia occurred in 15/83 (18.1%) patients. In contrast, low levels of immunoglobulins were found as follows: selective IgA deficiency 2/83 (2.4%), reduced IgG levels 7/83 (8.4%), reduced IgM 14/83 (16.9%). Only 1 patient required immunoglobulin replacement. Immunoglobulin abnormalities are frequently found in lupus nephritis, ranging from polyclonal hypergammaglobulinemia to hypogammglobulinemia. Consequently, immunoglobulin levels should be assessed prior to commencing BCTT.

  • Adverse infusion reactions to rituximab in systemic lupus erythematosus: a retrospective analysis
    BMC Rheumatol. (IF 0) Pub Date : 2019-08-29
    Ashleigh Hennessey; Joanna Lukawska; Geraldine Cambridge; David Isenberg; Maria Leandro

    To undertake a retrospective review of patients with SLE who had received Rituximab in order to determine the rates and associated patient characteristics of clinically significant adverse infusion reactions. A descriptive analysis was undertaken of each infusion reaction, which was then assessed using the clinical information available to hypothesise on the possible underlying mechanism(s). Records of 136 SLE patients previously treated with 481 individual infusions of Rituximab were reviewed. A total of 22 patients (17.6%) had 28 (5.8% of total infusions) documented clinically significant adverse infusion reactions. Average age at first Rituximab infusion in patients without a reaction was 37 years (range 16–73) compared with 30 years (range 18–56) in those with a reaction. A high proportion of men (18.2%) experienced an infusion reaction. Severity and type of reaction varied. 6.4% of those who had a reaction were not retreated. While Rituximab remains an important tool in the treatment of SLE it is important to be aware that rates of infusion reactions may be more significant in SLE than in other diseases. A prospective study is required to better characterise the reactions.

  • Which patient reported outcome domains are important to the rheumatologists while assessing patients with rheumatoid arthritis?
    BMC Rheumatol. (IF 0) Pub Date : 2019-09-05
    Aprajita Jagpal; Ronan O’Beirne; Melanie S. Morris; Bernadette Johnson; James Willig; Huifeng Yun; Andrea L. Cherrington; Liana Fraenkel; Jeffrey R. Curtis; Monika M. Safford; Iris Navarro-Millán

    Patient-reported outcomes (PROs) aid in rheumatoid arthritis (RA) management, but it is not well understood which measures would be most relevant to the rheumatologists for making treatment decisions. We recruited rheumatologists nationally to participate in moderated structured group teleconference discussions using the nominal group technique. Participants in each group generated lists of the elements from patient’s history and signs that they use to make treatment recommendations for RA. Each participant then selected the three most important elements from the generated list. The results of each group were then combined and summarized. Twenty-five rheumatologists participated in 4 groups (group size ranged from 4 to 8) and 150 available ranking votes across all groups. The statements generated across the 4 groups were categorized into 13 topics (including symptoms, physical function, comorbidities, social aspects, physical findings, response to treatment, treatment adherence, pain management, side effects, tests, access to care, contraception, and organ involvement), 10 of which received ranking votes. Symptoms received the highest ranking (46% of votes), followed by physical function (16%), and physical findings (13%). Among the unranked topics, social aspects had the highest number of statements (8 statements). Rheumatologists highly valued patient-reported RA symptoms and physical function to inform their treatment decisions, even above objective data such as physical findings and test results. These results can guide the selection of validated PRO measures to assess these domains to inform the clinical care of patients with rheumatoid arthritis.

  • Prevalence and associated factors of subclinical atherosclerosis in rheumatoid arthritis at the university hospital of Kinshasa
    BMC Rheumatol. (IF 0) Pub Date : 2019-09-09
    Christophe Mulumba; Pierrot Lebughe; Jean-Marie Mbuyi-Muamba; Jean-Robert Makulo; François Lepira; Jean Mukaya; Rene Westhovens; Patrick Verschueren; Jean-Jacques Malemba

    Rheumatoid arthritis (RA) is associated with a 5 to 10 years reduction in life expectancy due to premature atherosclerosis. This reduction is the consequence of traditional cardiovascular risk factors (TCRF) as well as systemic inflammation. The aim of the present study was to describe the prevalence and factors associated with subclinical atherosclerosis in RA at the University Hospital of Kinshasa (UHK). Patients with a diagnosis of RA based on the 2010 ACR/EULAR criteria were included in this cross-sectional study from 1 June 2014 to 31 May 2015 at the UHK. RA disease activity was measured using the DAS28-ESR. Active RA was defined by a DAS 28 > 2.6. Severe RA was defined by the presence of extra-articular manifestation, joint erosions on X-rays or HAQ ≥0.5. An assessment of subclinical atherosclerosis was performed by the measurement of the carotid intima-media thickness (cIMT) using two-dimensional ultrasonography. Subclinical atherosclerosis was defined by a cIMT ≥0.9 mm. A diagnosis of atheroma plaque was retained when the cIMT was ≥1.5 mm. The association between subclinical atherosclerosis and potential risk factors was modeled using logistic regression analysis. We recruited 75 patients. The average age was 51.8 ± 14.6 years, with a sex ratio F/M of 4. The prevalence of subclinical atherosclerosis was 32%. In logistic regression being a woman of ≥55 years old (aOR 10.6, 95% CI [2.087–53.82], p = 0.028), DAS28-ESR > 2.6 (aOR 3.5,95% CI [1.55–10.38], p = 0.044), severe RA (aOR 32.6,95% CI [1.761–60.37],p = 0.035), high blood pressure (aOR 22.4,95% CI [5.04–99.41], p = 0.005) and obesity (aOR 32.3, 95% CI [2.606–40.73], p = 0.026) emerged as factors associated with subclinical atherosclerosis. Subclinical atherosclerosis is common in RA patients attending the UHK. It appears to be associated with RA disease activity and severity apart from traditional cardiovascular risk factors. These results suggest that early management of subclinical atherosclerosis targeting remaining RA disease activity and cardiovascular risk factors could slow down progression to clinical cardiovascular disease.

  • Group B streptococcus is the most common pathogen for septic arthritis with unique clinical characteristics: data from 12 years retrospective cohort study
    BMC Rheumatol. (IF 0) Pub Date : 2019-09-16
    Rungkan Ruksasakul; Pongthorn Narongroeknawin; Paijit Assavatanabodee; Sumapa Chaiamnuay

    Group B Streptococcus (GBS) emerged as the frequent pathogen for septic arthritis. There was no study comparing risks, clinical presentations and outcomes between GBS septic arthritis and other bacterial septic arthritis. The aim of this study is to evaluate the differences in risks, clinical presentations, and outcomes of GBS septic arthritis and other bacterial septic arthritis, and identify independent risks and clinical presentations suggesting GBS septic arthritis. Medical records of patients diagnosed with non-gonococcal bacterial arthritis admitted in Phramongkutklao Hospital during 2006–2018 were reviewed. Associated risks, clinical presentations and outcomes were compared between GBS septic arthritis (GBS group) and other bacterial septic arthritis (other bacterial group). Two hundred and thirty one cases of non-gonococcal bacterial arthritis confirmed by positive joint fluid cultures and/or hemocultures were included. The three most common pathogens were GBS (37.7%), Staphylococcus aureus (23.4%) and Streptococcus viridans (7.4%). GBS group was more commonly found in rainy season than other bacterial group. Patients in GBS group were less likely to have underlying diseases and had more number of involved joints than those in other bacterial group. The clinical presentations more commonly found in GBS group than other bacterial group were oligo-polyarthritis, upper extremities joint involvement, axial joint involvement, tenosynovitis and central nervous system involvement. Multivariate analysis found the independent associated factors of GBS arthritis are tenosynovitis, oligo-polyarthritis and rainy season. GBS is now the most common pathogen for bacterial septic arthritis. The independent associated factors of GBS arthritis were oligo-polyarthritis, tenosynovitis and rainy season.

  • Trends in diagnostic prevalence and treatment patterns of male and female ankylosing spondylitis patients in the United States, 2006–2016
    BMC Rheumatol. (IF 0) Pub Date : 2019-09-23
    Jessica Walsh; Theresa Hunter; Krista Schroeder; David Sandoval; Rebecca Bolce

    There has been much variation between epidemiological studies that report the prevalence of ankylosing spondylitis (AS). This study aimed to analyze the diagnostic prevalence rates and treatment patterns of male and female AS patients in the United States adult insured population from 2006 to 2016. Trends in AS prevalence were calculated for the 11-year period covering January 1, 2006 to December 31, 2016. Adult (18+ years old) AS patients were included in this retrospective analysis of medical and pharmacy claims data from the IBM Marketscan Commercial, Medicaid and Medicare-Supplemental Claims database. Prevalence was determined as having ≥1 AS diagnostic codes (ICD-9:720.0; ICD-10:M45.x). Trends in treatment patterns were also analyzed and stratified by gender. The AS prevalence increased from 0.04 to 0.09% from 2006 to 2016. The mean age between 2006 and 2016 ranged from 49.52–50.00 years. In 2006, approximately 40% of AS patients were female, while in 2016 over 47% of AS patients were female. Rates of use of TNF inhibitors and oral glucocorticoids increased, while NSAIDs and non-biologic DMARDs (sulfasalazine & methotrexate) rates decreased. Opioid use rates were stable. In 2016, males were more likely to be prescribed biologics, while females were more likely to be prescribed methotrexate, sulfasalazine, NSAIDs, muscle relaxants, anticonvulsants, opioids, and glucocorticoids. The prevalence of AS diagnosis codes more than doubled between 2006 and 2016, but the very low prevalence suggests that AS continues to be underdiagnosed and under-addressed in routine clinical practice. Despite the increase in female AS patients, females were less likely to be prescribed biologics compared to male AS patients.

  • Development of ReproKnow, a reproductive knowledge assessment for women with rheumatic diseases
    BMC Rheumatol. (IF 0) Pub Date : 2019-10-21
    Mehret Birru Talabi; Megan E. B. Clowse; Susan J. Blalock; Galen Switzer; Lan Yu; Alaina Chodoff; Sonya Borrero

    The objective of this study was to develop an assessment tool, ReproKnow, to evaluate the reproductive health knowledge of women with a wide range of rheumatic diseases. The 10-item multiple-choice questionnaire was developed with feedback from a panel of content experts and female patients with rheumatic diseases. Construct validity using known-groups analysis was evaluated through comparison of median total ReproKnow scores between rheumatology fellows and nurses. Female patients aged 18–50 years were recruited to take ReproKnow and demographic questionnaires in two outpatient clinics. Associations between patients’ mean total knowledge scores and demographic characteristics were assessed using independent-sample t-tests. Questions were also categorized by topical area, and the percentages were calculated. The completion rate of questions in ReproKnow was 100% across all users. Median ReproKnow scores were significantly higher among rheumatology fellows than among nurses (p = 0.045). The 153 patients recruited to the study had at least one of 15 rheumatic diseases. Patients’ mean knowledge score was 5.05 (SD 2.24) out of a possible high score of 10. Patients who were younger, White, and more educated had significantly higher scores than did other patients (p’s < 0.05). Patients who bore children after their disease diagnosis had higher knowledge scores than did women whose children were born prior to their diagnosis; in contrast, women with histories of surgical sterilization or hysterectomy had lower knowledge scores than other women. Knowledge scores of women who used potentially fetotoxic medications did not vary from the remainder of the sample. Patients demonstrated gaps in knowledge about birth outcomes, contraceptive efficacy, and breastfeeding safety. Initial testing of ReproKnow suggests that it may be a promising tool to assess the reproductive health knowledge of women with diverse rheumatic diseases. Specific knowledge deficits elicited from ReproKnow may be important targets for future educational interventions.

  • A review of accelerometer-derived physical activity in the idiopathic inflammatory myopathies
    BMC Rheumatol. (IF 0) Pub Date : 2019-10-21
    Alexander Oldroyd; Max A. Little; William Dixon; Hector Chinoy

    The idiopathic inflammatory myopathies (IIMs) are a group of rare conditions characterised by muscle inflammation (myositis). Accurate disease activity assessment is vital in both clinical and research settings, however, current available methods lack ability to quantify associated variation of physical activity, an important consequence of myositis. This study aims to review studies that have collected accelerometer-derived physical activity data in IIM populations, and to investigate if these studies identified associations between physical and myositis disease activity. A narrative review was conducted to identify original articles that have collected accelerometer-derived physical activity data in IIM populations. The following databases were searched from February 2000 until February 2019: Medline via PubMed, Embase via OVID and Scopus. Of the 297 publications screened, eight studies describing accelerometer use in 181 IIM cases were identified. Seven out of the eight studies investigated juvenile dermatomyositis (JDM) populations and only one reported on an adult-onset population. Population sizes, disease duration, accelerometer devices used, body placement sites, and study duration varied between each study. Accelerometer-derived physical activity levels were reduced in IIM cohorts, compared to healthy controls, and studies reported improvement of physical activity levels following exercise programme interventions, thus demonstrating efficacy. Higher levels of accelerometer-derived physical activity measurements were associated with shorter JDM disease duration, current glucocorticoid use and lower serum creatine kinase. However, no clear association between muscle strength and accelerometer-derived physical activity measures was identified. The use of accelerometer-derived physical activity in IIM research is in its infancy. Whilst knowledge is currently limited to small studies, the opportunities are promising and future research in this area has the potential to improve disease activity assessment for clinical and research applications.

  • A systematic review of guidelines for managing rheumatoid arthritis
    BMC Rheumatol. (IF 0) Pub Date : 2019-10-22
    Aneela Mian; Fowzia Ibrahim; David L. Scott

    We systematically reviewed current guidelines for managing rheumatoid arthritis (RA) to evaluate their range and nature, assess variations in their recommendations and highlight divergence in their perspectives. We searched Medline and Embase databases using the terms ‘clinical practice guidelines’ and ‘rheumatoid arthritis’ from January 2000 to January 2017 together with publications of national and international bodies. We included guidelines providing recommendations on general RA management spanning a range of treatments and published in English. We undertook narrative assessments due to the heterogeneity of the guidelines. We identified 529 articles; 22 met our inclusion criteria. They were primarily developed by rheumatologists with variable involvement of patient and other experts. Three dealt with early RA, one established RA and 18 all patients. Most guidelines recommend regular assessments based on the Outcome Measures in Rheumatology core dataset; 18 recommended the disease activity score for 28 joints. Twenty recommended targeting remission; 16 suggested low disease activity as alternative. All guidelines recommend treating active RA; 13 made recommendations for moderate disease. The 21 guidelines considering early RA all recommended starting disease modifying drugs (DMARDs) as soon as possible; methotrexate was recommended for most patients. Nineteen recommended combination DMARDs when patients failed to respond fully to monotherapy and biologics were not necessarily indicated. Twenty made recommendations about biologics invariably suggesting their use after failing conventional DMARDs, particularly methotrexate. Most did not make specific recommendations about using one class of biologics preferentially. Eight recommended tapering biologics when patients achieved sustained good responses. Five general principles transcend most guidelines: DMARDs should be started as soon as possible after the diagnosis; methotrexate is the best initial treatment; disease activity should be regularly monitored; give biologics to patients with persistently active disease who have already received methotrexate; remission or low disease activity are the preferred treatment target.

  • Fibromyalgia in the workplace: risk factors for sick leave are related to professional context rather than fibromyalgia characteristics— a French national survey of 955 patients
    BMC Rheumatol. (IF 0) Pub Date : 2019-10-26
    F. Laroche; D. Azoulay; A. P. Trouvin; J. Coste; S. Perrot

    Work and workplace factors are important in fibromyalgia management. We investigated factors associated with sick leave in professionally active women living with fibromyalgia. A questionnaire for fibromyalgia patients in employment was developed by pain and occupational physicians and patients’ organizations. Women in full-time work, screened for fibromyalgia with the FiRST questionnaire, were recruited for a national online survey. Sick leave over the preceding year was analyzed. In 5 months, we recruited 955 women, with a mean of 37 days of sick leave in the previous year: no sick leave (36%), up to 1 month (38%), 1 to 2 months (14%), more than 2 months (12%). In the groups displayed no differences in demographic characteristics, fibromyalgia symptoms, functional severity and psychological distress were observed. However, they differed in workplace characteristics, commute time, stress and difficulties at work, repetitive work, noisy conditions, career progression problems and lack of recognition, which were strong independent risk factors for longer sick leave. Sedentary positions, an extended sitting position, heavy loads, exposure to thermal disturbances and the use of vibrating tools did not increase the risk of sick leave. Women with fibromyalgia frequently take sick leave, the risk factors for which are related to the workplace rather than fibromyalgia characteristics. This is the first study to assess the impact of occupational and clinical factors on sick leave in women living with fibromyalgia. Risk factors were found to be related to the workplace rather than fibromyalgia and personal characteristics. Workplace interventions should be developed for women with fibromyalgia.

  • The multifaceted impact of anxiety and depression on patients with rheumatoid arthritis
    BMC Rheumatol. (IF 0) Pub Date : 2019-10-28
    Steve Peterson; James Piercy; Stuart Blackburn; Emma Sullivan; Chetan S. Karyekar; Nan Li

    The prevalence of mood disturbances such as anxiety and depression is greater in rheumatoid arthritis (RA) patients than in the general population. Given this association, the primary aim of this study was to assess the incremental impact of anxiety or depression on patients with RA from the United States of America (USA) and Europe, independent of the impact of the underlying RA disease. Rheumatologists (n = 408) from the USA and 5 European countries completed patient record forms for a predetermined number of RA patients who consulted consecutively during the study period; these patients completed patient-reported questionnaires. Descriptive statistics and multivariate regression were used to investigate the relationship between anxiety and depression with treatment and economic outcomes in RA patients. Of 1015 physician and patient pairs who completed all relevant questionnaire sections, 390 (38.4%) patients self-reported anxiety or depression, while 180 (17.7%) patients were reported to have anxiety or depression by their physicians. Controlling for age, gender, body mass index and clinical factors (flaring and severity), multiple regression analyses suggested that patients with anxiety or depression more often experienced treatment dissatisfaction (odds ratio [OR] 2.28; P < .001), had greater impairment in work (coefficient [β] = 11.82; P = .001) and usual activity (β = 14.73; P < .001), greater disability (β = .35; P < .001), and more often reported unemployment (OR 1.74; P = .001). Multinomial logistic regression revealed discordance between physician and patient satisfaction with treatment. For patients reporting anxiety or depression, physicians were more often satisfied with achievement of current disease control than patients (relative risk ratio 2.19; P = .002). Concomitant anxiety or depression was associated with a significant incremental impact on the health-related quality of life and economic aspects of life of patients with RA. In light of observed differences between physician recognition of patient anxiety and/or depression versus patient reporting of anxiety and/or depression symptoms, further research is warranted to develop optimal screening and management of depression and anxiety in patients with RA.

  • Takayasu arteritis with pyoderma gangrenosum: case reports and literature review
    BMC Rheumatol. (IF 0) Pub Date : 2019-11-05
    Xuehan Zhang; Yang Jiao

    Takayasu arteritis is a rare, chronic inflammatory arteriopathy affecting mainly the aorta and its branches. Many skin manifestations have been reported in association with this disease. Pyoderma gangrenosum is a skin complication that is a neutrophilic dermatosis characterized by destructive, necrotizing and noninfective skin infiltration. However, there are no related records on these conditions in Chinese patients. We reported two Chinese female patients presenting with pyoderma gangrenosum associated with Takayasu arteritis. Pyoderma gangrenosum preceded Takayasu arteritis in both patients. Their skin lesions were diagnosed as pyoderma gangrenosum through skin biopsy and relieved after treating with steroids and immunosuppressants. During the follow-up, both patients developed symptoms caused by vascular stenosis and occlusion, such as dizziness and weakness of upper limb. The results of aortic angiography revealed multiple large arteries narrowed and blocked. According to the criteria of the American College of Rheumatology, the vasculitis in both patients were classified as Takayasu arteritis. Since there was scant evidence of active inflammation and the skin lesions were stable, neither of them was given strong immnosuppressive therapy. The PubMed database was also searched and 16 related well-documented cases of Takayasu with pyoderma gangrenosum were reviewed and summarized. Pyoderma gangrenosum could occur at any stage of the Takayasu arteritis disease process. No correlation was found between the location of the skin lesions and the clinical severity and scope of Takayasu arteritis. It is important to remember the rare possibility of Takayasu arteritis in patients with skin lesions indicative of pyoderma gangrenosum of unknown aetiology. Obtaining the relevant history and regular monitoring of the arteries are necessary.

  • Expert consensus on relevant risk predictors for the occurrence of osteoporotic fractures in specific clinical subgroups – Delphi survey
    BMC Rheumatol. (IF 0) Pub Date : 2019-11-12
    Nicolas S. Bodmer; Hans Jörg Häuselmann; Diana Frey; Daniel Aeberli; Lucas M. Bachmann

    There is an ongoing discussion about incorporating additional risk factors to established WHO fracture risk assessment tool (FRAX) to improve the prediction accuracy in clinical subgroups. We aimed to reach an expert consensus on possible additional predictive parameters for specific clinical subgroups. Two-round modified Delphi survey: We generated a shortlist of experts from the authors’ lists of the pertinent literature and complemented the list with experts known to the authors. Participants were asked to name possible relevant risk factors besides the FRAX-parameters for the occurrence of osteoporotic fractures. Experts specified these possible predictors for specific subgroups of patients. In the second round the expert panel was asked to weight each parameter of every subgroup assigning a number between one (not important) to ten (very important). We defined the threshold for an expert consensus if the interquartile range (IQR) of a predictor was ≤2. The cut-off value of the median attributed weights for a relevant predictor was set at ≥7. Eleven experts of seven countries completed both rounds of the Delphi. The participants agreed on nine additional parameters for seven categories. For the category “secondary osteoporosis”, “older adults” and “nursing home patients”, there was a consensus that history of previous falls was relevant, while for men and postmenopausal women, there was a consensus that the spine fracture status was important. For the group “primary and secondary osteoporosis” the experts agreed on the parameters “high risk of falls”, “lumbar spine bone mineral density (BMD)” and “sarcopenia”. This Delphi survey reached a consensus on various parameters that could be used to refine the currently existing FRAX for specific clinical situations or patient groups. The results may be useful for studies aiming at improving the predictive properties of instruments for fracture prediction.

  • Disease activity flares and pain flares in an early rheumatoid arthritis inception cohort; characteristics, antecedents and sequelae
    BMC Rheumatol. (IF 0) Pub Date : 2019-11-18
    Daniel F. McWilliams; Shimin Rahman; Richard J. E. James; Eamonn Ferguson; Patrick D. W. Kiely; Adam Young; David A. Walsh

    RA flares are common and disabling. They are described in terms of worsening inflammation but pain and inflammation are often discordant. To inform treatment decisions, we investigated whether inflammatory and pain flares are discrete entities. People from the Early RA Network (ERAN) cohort were assessed annually up to 11 years after presentation (n = 719, 3703 person-years of follow up). Flare events were defined in 2 different ways that were analysed in parallel; DAS28 or Pain Flares. DAS28 Flares satisfied OMERACT flare criteria of increases in DAS28 since the previous assessment (≥1.2 points if active RA or ≥ 0.6 points if inactive RA). A ≥ 4.8-point worsening of SF36-Bodily Pain score defined Pain Flares. The first documented episode of each of DAS28 and Pain Flare in each person was analysed. Subgroups within DAS28 and Pain Flares were determined using Latent Class Analysis. Clinical course was compared between flare subgroups. DAS28 (45%) and Pain Flares (52%) were each common but usually discordant, with 60% of participants in DAS28 Flare not concurrently in Pain Flare, and 64% of those in Pain Flare not concurrently in DAS28 Flare. Three discrete DAS28 Flare subgroups were identified. One was characterised by increases in tender/swollen joint counts (14.4%), a second by increases in symptoms (13.1%), and a third displayed lower flare severity (72.5%). Two discrete Pain Flare subgroups were identified. One occurred following low disease activity and symptoms (88.6%), and the other occurred on the background of ongoing active disease and pain (11.4%). Despite the observed differences between DAS28 and Pain Flares, each was associated with increased disability which persisted beyond the flare episode. Flares are both common and heterogeneous in people with RA. Furthermore our findings indicate that for some patients there is a discordance between inflammation and pain in flare events. This discrete flare subgroups might reflect different underlying inflammation and pain mechanisms. Treatments addressing different mechanisms might be required to reduce persistent disability after DAS28 and Pain Flares.

  • Serious infections in patients with self-reported psoriatic arthritis from the Psoriasis Longitudinal Assessment and Registry (PSOLAR) treated with biologics
    BMC Rheumatol. (IF 0) Pub Date : 2019-11-28
    Christopher T. Ritchlin; Mona Stahle; Yves Poulin; Jerry Bagel; Soumya D. Chakravarty; Shelly Kafka; Bhaskar Srivastava; Wayne Langholff; Alice B. Gottlieb

    Patients with psoriatic arthritis (PsA) have increased risk of adverse events, including serious infections (SI), compared with psoriasis patients. Patients eligible for, or receiving conventional systemic and biologic agents for psoriasis were followed prospectively using PSOLAR. Cohorts included: ustekinumab, tumor necrosis factor (TNF) inhibitors; infliximab; etanercept; adalimumab; non-biologic/methotrexate (MTX) (reference group); and non-biologic/non-MTX. Multivariate analyses using Cox hazard regression were used to identify factors associated with time to first SI. Rates of SI in PSOLAR psoriasis patients with self-reported PsA and possible risks with biologic therapy were evaluated. PSOLAR enrolled 4315 psoriasis patients with self-reported PsA. The overall population (N = 2401) included patients (n): 628 ustekinumab; 1413 TNF inhibitors; 258 infliximab; 481 etanercept; 674 adalimumab; 54 other biologics, 98 non-biologic/MTX; 208 non-biologic/non-MTX. Overall, 138 SI were reported with incidence rates per 100 patient-years as follows: a) ustekinumab: 1.00; b) TNF inhibitors: 2.22; c) infliximab: 2.12; d) etanercept: 2.58; e) adalimumab: 1.99; f) non-biologic/MTX: 3.01; g) and non-biologic/non-MTX: 2.31. Age, time-dependent disease activity Physician’s Global Assessment (PGA) of 4, 5, history of infection, and diabetes were associated with increased risk for SI (p < 0.05) in self-reported PsA patients. Biologic groups, other than ustekinumab, had numerically higher rates of SI. PSOLAR psoriasis patients with self-reported PsA in the TNF inhibitors, infliximab, adalimumab, etanercept, and MTX cohorts had numerically higher SI rates than the ustekinumab cohort, although not statistically significant. Age, PGA 4, 5, history of infection, and diabetes were associated with an increased risk for SI, irrespective of biologic exposure. NCT00508547; Registered July 30, 2007.

  • Rheumatoid Arthritis Portrayal by UK National Newspapers 2011-2016: A Service User - Led Thematic Analysis of Language Used.
    BMC Rheumatol. (IF 0) Pub Date : 2019-03-20
    Andrew Mark Bassett,Savia de Souza,Ruth Williams,Heidi Lempp

    Background An important source of knowledge, beliefs, and attitudes about illness is the mass media. Research has established the often negative and emotive language utilised by journalists to report on physical and mental long-term illnesses. The limited amount of research on rheumatological conditions has largely focused on the extent of, and/or accuracy of media coverage. This is the first published study to examine systematically the language used by the United Kingdom (UK) popular press to specifically describe rheumatoid arthritis (RA). Methods A patient and public involvement (PPI) approach, involving academics and service users with RA, was used to conduct the research. LexisNexis online repository of print media was searched for articles within a defined five year time frame, which included RA in the headline and/or lead paragraph of 15 UK national non-specialist newspapers. Resultant articles were uploaded to NVivo, and a realist perspective aided a thematic analysis of the data set. Results A search of LexisNexis produced 413 newspaper articles, of which 147 met the inclusion criteria. Three themes emerged: (1) language used to describe RA; (2) language used to refer to those who live with RA and; (3) language used to report on potential new treatments for RA. Negative and emotive terms such as 'attack', 'painful', 'crippling', and 'agony' were the most frequently used to describe the experience of RA. People diagnosed with RA were often portrayed as 'sufferers' or 'victims', though neutral language was also deployed. 'Hope' and 'breakthrough' were the most reported terms for potential new treatments for RA. Across the three themes, tabloid and middle market newspaper articles applied more sensationalised language with attention grabbing headlines and news stories. By contrast, such emotive terminology was less apparent in broadsheets. Conclusions The media is a source of information about RA for the general population, but the quality of newspaper journalism about the condition requires improvement. The findings may act as a stimulus for a national public awareness initiative and/or social marketing campaign. How the language currently constructed to describe RA in the press is received by people with RA would be an important area for future research.

  • Trends in incidence, mortality, and causes of death associated with systemic sclerosis in Denmark between 1995 and 2015: a nationwide cohort study.
    BMC Rheumatol. (IF 0) Pub Date : 2019-03-20
    Sheraz A Butt,Jørgen L Jeppesen,Christine Fuchs,Mette Mogensen,Merete Engelhart,Christian Torp-Pedersen,Gunnar H Gislason,Søren Jacobsen,Charlotte Andersson

    Background To investigate the incidence and the mortality-rates of systemic sclerosis (SSc), its primary causes of death, and the temporal trends in events in Denmark during the last decades. Methods Using the Danish National Patient Registry, we identified all persons aged ≥18 years with a first-time diagnosis of SSc (ICD-10 code M34, excluding M34.2) between 1995 and 2015. Results A total of 2778 incident SSc cases were identified. The mean age at time of SSc diagnosis was 56 (standard deviation 15) years and 76% were women. The overall incidence rate (per 1,000,000 person-years) of diagnosed SSc was 24.4 (95% confidence interval 23.6-25.4), with a slight increase over the study period, age- and sex-adjusted incidence rate ratio 1.02 (95% confidence interval 1.01-1.02) per 1-year increase. The 1-year all-cause mortality rate per 100 person-years decreased from 6.1 (3.1-12.2) in 1995 to 5.3 (2.5-11.1) in 2015, sex- and age-adjusted hazard ratio 0.96 (95% CI 0.94-0.98) per 1-year increase. Over the period, the average age at SSc diagnosis increased and the proportion of women decreased, whereas the burden of comorbidities increased. One fifth of all deaths were attributable to cardiovascular causes, a fourth to pulmonary diseases, and 15% were due to cancer. Conclusions Within the last few decades, the incidence of SSc has increased and the 1-year mortality rate has decreased slightly in Denmark. Almost half of all deaths were attributable to cardiopulmonary causes.

  • A proteomic analysis of serum-derived exosomes in rheumatoid arthritis.
    BMC Rheumatol. (IF 0) Pub Date : 2019-03-20
    Hirotaka Tsuno,Mitsumi Arito,Naoya Suematsu,Toshiyuki Sato,Atsushi Hashimoto,Toshihiro Matsui,Kazuki Omoteyama,Masaaki Sato,Kazuki Okamoto,Shigeto Tohma,Manae S Kurokawa,Tomohiro Kato

    Background To understand the roles of serum exosomes in rheumatoid arthritis (RA), we comprehensively investigated the protein profiles of serum exosomes in patients with RA. Methods Exosomes were isolated from serum samples obtained from 33 patients (12 with active RA [aRA], 11 with inactive RA [iRA], 10 with osteoarthritis [OA]) and 10 healthy donors (HLs). Proteins extracted from the exosomes were separated by two-dimensional differential gel electrophoresis (2D-DIGE) and identified by mass spectrometry. Results In total, 204 protein spots were detected by 2D-DIGE. In the aRA, iRA, and OA groups, 24, 5, and 7 spots showed approximately ≥ ±1.3-fold intensity differences compared with the HL group, respectively. We were able to identify proteins in six protein spots. Among them, the protein spot identified as Toll-like receptor 3 (TLR3) showed approximately 6-fold higher intensity in the aRA group than in the other groups. Conclusions Patients with active RA possessed considerably different protein profiles of serum exosomes from patients with iRA, patients with OA, and healthy donors. The unique protein profile of serum exosomes, such as the possession of abundant TLR3 fragments, may reflect the pathophysiology of active RA.

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