Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
25105978 An osteoprotegerin gene polymorphism is associated with an increased risk of hip fracture 2014 INTRODUCTION: Patients with rheumatoid arthritis (RA) have a higher prevalence of osteoporosis and hip fracture than healthy individuals. Multiple genetic loci for osteoporotic fracture were identified in recent genome-wide association studies. The purpose of this study was to identify genetic variants associated with the occurrence of hip fracture in Japanese patients with RA. METHODS: DNA samples from 2,282 Japanese patients with RA were obtained from the DNA collection of the Institute of Rheumatology Rheumatoid Arthritis cohort (IORRA) study. Six single nucleotide polymorphisms (SNPs) that have been reported to be associated with fractures in recent studies were selected and genotyped. Forty hip fractures were identified with a maximum follow-up of 10 years. The genetic risk for hip fracture was examined using a multivariate Cox proportional hazards regression model. RESULTS: The risk analyses revealed that patients who are homozygous for the major allele of SNP rs6993813, in the OPG locus, have a higher risk for hip fracture (hazard ratio [95% CI] = 2.53 [1.29-4.95], P = 0.0067). No association was found for the other SNPs. CONCLUSIONS: Our results indicate that an OPG allele is associated with increased risk for hip fracture in Japanese patients with RA.
25172240 Clinical characteristics and risk factors for low dose methotrexate toxicity: a cohort of 2014 Nov OBJECTIVE: Low dose (10-25 mg/week) methotrexate is widely used for the management of systemic inflammatory diseases, and is considered to be relatively safe. Toxicity due to low dose MTX has been reported but is poorly characterized. We describe the clinical features, risk factors, and outcomes of low dose MTX toxicity in a large case series at our center. PATIENTS AND METHODS: We conducted a retrospective case series of all adult (>18 years) patients hospitalized at Sheba Medical Center, between 2005 and 2012 for low dose MTX toxicity. RESULTS: We identified 28 patients (age: 70.4±13.7 years, range: 33-88; 20 (71%) females) hospitalized for low dose MTX toxicity. Indications for MTX therapy included: rheumatoid arthritis (39.2%), psoriasis±arthritis (21.5%), polymyalgia rheumatica (10.8%) and other inflammatory conditions (28.5%). Pancytopenia was the most common manifestation of low dose MTX toxicity detected in 78.5% of the patients. Potential risk factors included acute renal failure, hypoalbuminemia, concurrent use of drugs known to interact with MTX, and dose errors. Serum MTX concentrations (n=20, mean 0.04±0.07 μg/mL range: 0-0.3) did not correlate with the degree of either neutropenia (r=-0.36; p=0.18) or thrombocytopenia (r=0.44; p=0.10). Seven (25%) patients died, all from pancytopenia followed by sepsis. Serum MTX concentrations did not differ between the patients who died from MTX toxicity (n=6; mean: 0.05±0.04 μg/mL) and those who survived the toxicity (n=14 mean 0.04±0.08; p=0.45). CONCLUSIONS: Low-dose MTX toxicity can be life threatening, mainly due to myelosuppression. There is no rationale for MTX therapeutic drug monitoring in the setting of low-dose toxicity.
24810700 Rheumatoid myositis leading to acute lower extremity compartment syndrome: a case-based re 2015 Oct Muscle pain and weakness in a rheumatoid arthritis (RA) patient has a broad differential, and myositis should be considered early in the disease course as serious limb and life-threatening sequelae may occur. A 55-year-old woman with a past medical history of methotrexate-controlled RA presented with right leg pain for 4 days. The patient suffered sensory loss in the right foot and decreased strength in the toes. Lab tests revealed elevated creatine kinase, ESR, and anti-rheumatoid factor antibody titers. CT scan revealed myositis of posterior compartment muscles. Progressive edema, pain, and neuromuscular deficits persisted despite steroid and antibiotic therapy, so the patient was taken for urgent fasciotomy for acute compartment syndrome. The muscle biopsy showed diffuse mononuclear cell infiltration as well as perivascular and perineural involvement consistent with rheumatoid myositis (RM). The patient did well post-op on a prednisone taper. This case underlines the systemic nature of RA and exemplifies the severity of inflammation that may lead to grave consequences such as compartment syndrome. The histopathology is diagnostic when there is evidence of mononuclear cell infiltration; however, this is not entirely specific. Early, aggressive therapy with immunosuppressives is warranted in such patients. RM has not, to our knowledge, been recorded to cause acute compartment syndrome. Clinicians should be aware of this uncommon manifestation of RA keeping the various presentations of rheumatoid disease in mind when faced with these patients.
24758073 [Etanercept combined with Tripterygium wilfordii polyglycoside for treatment of rheumatoid 2014 Mar OBJECTIVE: To evaluate the efficacy and safety of etanercept plus Tripterygium wilfordii polyglycoside (TWP) in elderly patients with active rheumatoid arthritis (RA). METHODS: Totally 46 elderly patients with active RA were randomly assigned to the treatment group (22 cases) and the control group (24 cases). All patients received subcutaneous injection of etanercept, 25 mg each time, twice per week. The dosage was reduced to once per week 3 months later. Patients in the treatment group took TWP Tablet (10 mg each time, three times per day), while those in the control group took methotrexate (MTX), 10 mg each time, once per week. The whole course lasted for 24 weeks. Patients' rest pain, tender joint number, swollen joint number, health assessment questionnaire (HAQ), patients' global assessment, physicians' global assessment, erythrocyte sediment rate (ESR), C reactive protein (CRP), rheumatic factor were assessed at week 0, 4, 8, 12, and 24. The curative effect was statistically evaluated by the United States Institute of Rheumatology ACR20, ACR50, and ACR70 improvement criteria. Meanwhile, any adverse event was recorded and evaluated. RESULTS: Totally 41 completed the trial, and 5 dropped off (3 in the treatment group and 2 in the control group). Compared with the control group, there was no statistical difference in ACR20, ACR50, or ACR70 in the treatment group (P > 0.05). Compared with before treatment in the same group, there was some improvement in tender joint number, swollen joint number, visual analogue scale (VAS) for patients' global assessment, VAS for physicians' global assessment, ESR, CRP, and HAQ between the two groups, showing statistical difference (P < 0.05). Compared with the control group in the same phase, there was no statistical difference in the treatment group (P > 0.05). There was no statistical difference in the occurrence of adverse events between the two groups. CONCLUSIONS: Etanercept plus TWP could achieve equivalent therapeutic effect to that of Etanercept plus MTX. The two regimens could improve clinical signs, symptoms, and QOL related to RA. They were well tolerated in the treatment of elderly patients with active RA.
23401601 Efficacy and safety of leflunomide in DMARD-naive patients with early rheumatoid arthritis 2013 Jun OBJECTIVE: To assess the efficacy of LEF administered with or without a loading dose in DMARD-naïve patients with early RA. METHODS: This multicentre, double-blind, randomized clinical trial included adults with RA diagnosed within 6 months (ACR criteria). Patients were randomly selected to receive either a 100 mg loading dose or a 20 mg fixed dose of LEF for 3 days, followed by a 3-month open-label maintenance period of 20 mg LEF qd. The primary outcome criterion was ACR20 response rate at study end in the intent-to-treat population. Secondary criteria were ACR20, ACR50, ACR70 and DAS28 response rates at 1 and 3 months and safety. RESULTS: The intent-to-treat population included 120 patients (median time since diagnosis 0.95 months). The ACR20 response rate at study end was 69.0% (95%CI 60.5%, 77.4%). Response rates were significantly lower (P = 0.025) in the loading-dose group [58.5% (45.2%, 71.8%)] than in the fixed-dose group [77.8% (67.5%, 88.0%)]. Three-month ACR50, ACR70 and DAS28 response rates were 41.4%, 17.7% and 81.7%, respectively, with no significant differences between groups. Adverse events occurred in 53.7% (loading-dose group) and 49.3% (fixed-dose group) of patients, most frequently diarrhoea and elevated hepatic enzymes; these occurred more frequently and earlier in treatment when the loading dose was used. CONCLUSION: LEF was effective in DMARD-naïve patients with early disease. No incremental benefit was observed with the use of a loading dose, which may be associated with an increased initial rate of adverse events. The advantage of LEF initiation with a loading dose is not confirmed in this population. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00596206.
25166859 From synovial tissue to peripheral blood: myeloid related protein 8/14 is a sensitive biom 2014 OBJECTIVE: The change in number of CD68-positive sublining macrophages in serial synovial biopsies has been successfully used to discriminate on the group level between effective and ineffective treatment during early drug development in rheumatoid arthritis (RA) patients. Measurement of a soluble biomarker would clearly have practical advantages. Therefore, we investigated the sensitivity to change of myeloid related protein (MRP)8/14 in serum. METHODS: 139 RA patients who received known effective biologics (infliximab, adalimumab and rituximab) and 28 RA patients who received placebo/ineffective therapies were included. MRP8/14 levels were analyzed in baseline and follow-up serum samples and the standardized response mean (SRM) was calculated to determine the sensitivity to change of MRP8/14 in comparison to C-reactive protein (CRP) levels and the disease activity score evaluated in 28 joints (DAS28). RESULTS: In patients treated with effective treatment, the SRM for MRP8/14 was moderate (0.56), but in patients treated with placebo/ineffective treatment the SRM was 0.06, suggesting that this biomarker is perhaps not susceptible to placebo effects in proof-of-concept studies of relatively short duration. In contrast, the SRM for DAS28 was high for effective treatment (1.07), but also moderate for ineffective treatment (0.58), representing the placebo effect. The SRM for CRP was low in the effective (0.33) and ineffective (0.23) treatment groups. CONCLUSION: These data support the notion that quantification of changes in MRP8/14 serum levels could be used to predict potential efficacy of novel antirheumatic drugs in an early stage of drug development. A positive result would support the rationale for larger, conventional clinical trials to determine whether the effects are clinically relevant.
24439185 [Peptidyl arginine deiminase 4 participates in the pathogenesis of rheumatoid arthritis by 2013 Nov OBJECTIVE: To explore the probable function of peptidyl arginine deiminase 4 (PAD4) in rheumatoid arthritis(RA). METHODS: Real-time quantitative polymerase chain reaction (PCR) was used to determine the expression of PAD4 mRNA in peripheral blood mononucleated cells (PBMCs) from 60 RA patients and 40 healthy individuals. Asymmetric di-methylation of histone H3R17, symmetric di-methylation and mono-methylation of H4R3 were semi-quantified by Western blotting in 12 patients with osteoarthritis (OA), 26 patients with RA and 10 healthy controls. RESULTS: PAD4 mRNA in RA was significantly higher than that in healthy controls[34.6(16.7, 70.8) vs 20.6(11.1, 51.8), P < 0.05]. The level of histone H3R17 asymmetric di-methylation in RA was significantly higher than that of OA or control groups (71.34 ± 25.65 vs 37.18 ± 18.62 vs 50.67 ± 13.99, P < 0.01) , which was positively related to Tender joint count and Swollen joint count in 28 joints (r = 0.418, P = 0.034;r = 0.402, P = 0.042). The level of histone H4R3 symmetric di-methylation was similar in RA,OA and control groups (75.02 ± 20.35 vs 57.92 ± 22.77 vs 68.37 ± 17.57, P > 0.05) . The level of histone H4R3 mono-methylation in RA patients was significantly lower than that of OA patients and healthy individuals (11.24 ± 7.81 vs 32.77 ± 30.77 vs 51.20 ± 47.14, P < 0.05). The level of histone H4R3 mono-methylation in RA patients was negatively correlated to PAD4 (r = -0.643, P < 0.01) . The level of histone H3R17 asymmetric di-methylation and H4R3 symmetric di-methylation was not associated with PAD4 level in RA group (r = -0.185, P = 0.377; r = 0.198, P = 0.344). CONCLUSIONS: The level of histone H3R17 asymmetric di-methylation is significantly higher and the level of histone H4R3 mono-methylation is significantly lower in RA patients comparing with OA and control groups. Abnormality of histone methylation may be one of the mechanisms for the development of RA. PAD4 probably plays an important role in rheumatoid arthritis by influencing histone methylation.
24470443 Predictors of stopping and starting disease-modifying antirheumatic drugs for rheumatoid a 2014 Aug OBJECTIVE: Disease-modifying antirheumatic drugs (DMARDs) are the standard of care for rheumatoid arthritis (RA); however, studies have found that many patients do not receive them. We examined predictors of starting and stopping DMARDs among a longitudinal cohort of patients with RA. METHODS: Study participants came from a cohort of RA patients recruited from a random sample of rheumatologists' practices in Northern California. We examined patterns and predictors of stopping and starting nonbiologic and biologic DMARDs during 1982-2009 based on annual questionnaires. Stopping was defined as stopping all DMARDs and starting was defined as transitioning from no DMARDs to any DMARDs across 2 consecutive years. RESULTS: The analysis of starting DMARDs included 471 subjects with 1,974 pairs of years with no DMARD use in the first of 2 consecutive years. From this population, subjects started DMARD use by year 2 in 313 (15.9%) of the pairs. The analysis of stopping DMARDs included 1,026 subjects with 7,595 pairs of years with DMARD use in the first of 2 consecutive years; in 423 pairs (5.6%), subjects stopped DMARD use by year 2. In models that adjusted for RA-related factors, sociodemographics, and comorbidities, significant predictors of starting DMARDs included younger age, Hispanic ethnicity, shorter disease duration, and the use of oral glucocorticoids. In separate adjusted models, predictors of stopping DMARDs included Hispanic ethnicity and low income, while younger age was associated with a reduced risk of stopping. CONCLUSION: Efforts to improve DMARD use should focus on patient age, ethnicity, and income and RA-related factors.
24187110 Effectiveness and safety of tocilizumab: postmarketing surveillance of 7901 patients with 2014 Jan OBJECTIVE: An all-patient postmarketing surveillance program was conducted to evaluate the safety and effectiveness of tocilizumab (TCZ) for rheumatoid arthritis (RA) in the real-world clinical setting in Japan. METHODS: Patients received 8 mg/kg TCZ every 4 weeks and were observed for 28 weeks. Data were collected on patient characteristics, and drug safety and effectiveness. RESULTS: A total of 7901 patients were enrolled. Percentages of total and serious adverse events (AE) were 43.9% and 9.6%, respectively. The most common serious AE were infections (3.8%). Logistic regression analysis identified the following risk factors for the development of serious infection: age ≥ 65 years, disease duration ≥ 10 years, previous or concurrent respiratory disease, and concomitant corticosteroid dose > 5 mg/day (prednisolone equivalent). The incidence rate of serious infections in patients with ≥ 3 risk factors was 11.2%, compared with 1.2% for patients without risk factors. The Week 28 rates of 28-joint Disease Activity Score-erythrocyte sedimentation rate remission, Boolean remission, and European League Against Rheumatism (EULAR) Good Response were 47.6%, 15.1%, and 59.4%, respectively. Contributing factors for effectiveness were body weight ≥ 40 kg, less advanced RA, no previous biologics, no concomitant corticosteroids or nonsteroidal antiinflammatory drugs, and low disease activity at baseline. From the benefit-risk balance analysis, patients with a high probability of remission and a low probability of developing serious infection were most likely to have less advanced RA and to have not received biologics previously. CONCLUSION: These data confirm the safety and effectiveness of TCZ in patients with RA in the real-world clinical setting in Japan and identify factors that contribute to the successful use of TCZ for RA.
24986846 Adipose depots, not disease-related factors, account for skeletal muscle insulin sensitivi 2014 Oct OBJECTIVE: In prior reports, individuals with rheumatoid arthritis (RA) exhibited increased insulin resistance. However, those studies were limited by either suboptimal assessment methods for insulin sensitivity or a failure to account for important determinants such as adiposity and lack of physical activity. Our objectives were to carefully assess, compare, and determine predictors of skeletal muscle insulin sensitivity in RA, accounting for adiposity and physical activity. METHODS: Thirty-nine individuals with established (seropositive or erosions) and treated RA and 39 controls matched for age, sex, race, body mass index, and physical activity underwent a frequently sampled intravenous glucose tolerance test to determine insulin sensitivity. Inflammation, body composition, and physical activity were assessed with systemic cytokine measurements, computed tomography scans, and accelerometry, respectively. Exclusions were diabetes, cardiovascular disease, medication changes within 3 months, and prednisone use over 5 mg/day. This investigation was powered to detect a clinically significant, moderate effect size for insulin sensitivity difference. RESULTS: Despite elevated systemic inflammation [interleukin (IL)-6, IL-18, tumor necrosis factor-α; p < 0.05 for all], persons with RA were not less insulin sensitive [SI geometric mean (SD): RA 4.0 (2.4) vs control 4.9 (2.1)*10(-5) min(-1)/(pmol/l); p = 0.39]. Except for visceral adiposity being slightly greater in controls (p = 0.03), there were no differences in body composition or physical activity. Lower insulin sensitivity was independently associated with increased abdominal and thigh adiposity, but not with cytokines, disease activity, duration, disability, or disease-modifying medication use. CONCLUSION: In established and treated RA, traditional risk factors, specifically excess adiposity, play more of a role in predicting skeletal muscle insulin sensitivity than do systemic inflammation or other disease-related factors.
24040061 Power Doppler ultrasound phenotyping of expanding versus collapsed popliteal lymph nodes i 2013 Rheumatoid arthritis is a chronic inflammatory disease manifested by episodic flares in affected joints that are challenging to predict and treat. Longitudinal contrast enhanced-MRI (CE-MRI) of inflammatory arthritis in tumor necrosis factor-transgenic (TNF-Tg) mice has demonstrated that popliteal lymph nodes (PLN) increase in volume and contrast enhancement during the pre-arthritic "expanding" phase of the disease, and then suddenly "collapse" during knee flare. Given the potential of this biomarker of arthritic flare, we aimed to develop a more cost-effective means of phenotyping PLN using ultrasound (US) imaging. Initially we attempted to recapitulate CE-MRI of PLN with subcutaneous footpad injection of US microbubbles (DEFINITY®). While this approach allowed for phenotyping via quantification of lymphatic sinuses in PLN, which showed a dramatic decrease in collapsed PLN versus expanding or wild-type (WT) PLN, electron microscopy demonstrated that DEFINITY® injection also resulted in destruction of the lymphatic vessels afferent to the PLN. In contrast, Power Doppler (PD) US is innocuous to and efficiently quantifies blood flow within PLN of WT and TNF-Tg mice. PD-US demonstrated that expanding PLN have a significantly higher normalized PD volume (NPDV) versus collapsed PLN (0.553 ± 0.007 vs. 0.008 ± 0.003; p<0.05). Moreover, we define the upper (>0.030) and lower (<0.016) quartile NPDVs in this cohort of mice, which serve as conservative thresholds to phenotype PLN as expanding and collapsed, respectively. Interestingly, of the 12 PLN phenotyped by the two methods, there was disagreement in 4 cases in which they were determined to be expanding by CE-MRI and collapsed by PD-US. Since the adjacent knee had evidence of synovitis in all 4 cases, we concluded that the PD-US phenotyping was correct, and that this approach is currently the safest and most cost-effective in vivo approach to phenotype murine PLN as a biomarker of arthritic flare.
23547211 Cardiovascular events are not associated with MTHFR polymorphisms, but are associated with 2013 Jun OBJECTIVE: C677T and A1298C polymorphisms in the enzyme methylenetetrahydrofolate reductase (MTHFR) have been associated with increased cardiovascular (CV) events in non-rheumatoid arthritis (RA) populations. We investigated potential associations of MTHFR polymorphisms and use of methotrexate (MTX) with time-to-CV event in data from the Veterans Affairs Rheumatoid Arthritis (VARA) registry. METHODS: VARA participants were genotyped for MTHFR polymorphisms. Variables included demographic information, baseline comorbidities, RA duration, autoantibody status, and disease activity. Patients' comorbidities and outcome variables were defined using International Classification of Diseases-9 and Current Procedural Terminology codes. The combined CV event outcome included myocardial infarction (MI), percutaneous coronary intervention, coronary artery bypass graft surgery, and stroke. Cox proportional hazards regression was used to model the time-to-CV event. RESULTS: Data were available for 1047 subjects. Post-enrollment CV events occurred in 97 patients (9.26%). Although there was a trend toward reduced risk of CV events, MTHFR polymorphisms were not significantly associated with time-to-CV event. Time-to-CV event was associated with prior stroke (HR 2.01, 95% CI 1.03-3.90), prior MI (HR 1.70, 95% CI 1.06-2.71), hyperlipidemia (HR 1.57, 95% CI 1.01-2.43), and increased modified Charlson-Deyo index (HR 1.23, 95% CI 1.13-1.34). MTX use (HR 0.66, 95% CI 0.44-0.99) and increasing education (HR 0.87, 95% CI 0.80-0.95) were associated with a lower risk for CV events. CONCLUSION: Although MTHFR polymorphisms were previously associated with CV events in non-RA populations, we found only a trend toward decreased association with CV events in RA. Traditional risk factors conferred substantial CV risk, while MTX use and increasing years of education were protective.
22562972 Adalimumab: long-term safety in 23 458 patients from global clinical trials in rheumatoid 2013 Apr BACKGROUND: As long-term treatment with antitumour necrosis factor (TNF) drugs becomes accepted practice, the risk assessment requires an understanding of anti-TNF long-term safety. Registry safety data in rheumatoid arthritis (RA) are available, but these patients may not be monitored as closely as patients in a clinical trial. Cross-indication safety reviews of available anti-TNF agents are limited. OBJECTIVE: To analyse the long-term safety of adalimumab treatment. METHODS: This analysis included 23 458 patients exposed to adalimumab in 71 global clinical trials in RA, juvenile idiopathic arthritis, ankylosing spondylitis (AS), psoriatic arthritis, psoriasis (Ps) and Crohn's disease (CD). Events per 100 patient-years were calculated using events reported after the first dose through 70 days after the last dose. Standardised incidence rates for malignancies were calculated using a National Cancer Institute database. Standardised death rates were calculated using WHO data. RESULTS: The most frequently reported serious adverse events across indications were infections with greatest incidence in RA and CD trials. Overall malignancy rates for adalimumab-treated patients were as expected for the general population; the incidence of lymphoma was increased in patients with RA, but within the range expected in RA without anti-TNF therapy; non-melanoma skin cancer incidence was raised in RA, Ps and CD. In all indications, death rates were lower than, or equivalent to, those expected in the general population. CONCLUSIONS: Analysis of adverse events of interest through nearly 12 years of adalimumab exposure in clinical trials across indications demonstrated individual differences in rates by disease populations, no new safety signals and a safety profile consistent with known information about the anti-TNF class.
24390342 Genetics of rheumatoid arthritis contributes to biology and drug discovery. 2014 Feb 20 A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ∼10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2 - 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation, cis-acting expression quantitative trait loci and pathway analyses--as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes--to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
23044729 Ultrasound joint inflammation in rheumatoid arthritis in clinical remission: how many and 2013 Apr OBJECTIVE: To investigate the sensitivity for detecting subclinical synovitis of different reduced joint ultrasound (US) assessment models as compared with a comprehensive US assessment in rheumatoid arthritis (RA) patients in clinical remission. METHODS: Sixty-seven RA patients (50 women, 17 men) in clinical remission as judged by their consultant rheumatologist and treated with methotrexate were prospectively recruited. Patients were evaluated for disease activity according to the Disease Activity Score in 28 joints (DAS28) and the Simplified Disease Activity Index (SDAI) by the same investigator. Each patient underwent a 44-joint B-mode and power Doppler (PD) assessment by a rheumatologist blinded to the clinical and laboratory data. B-mode synovial hypertrophy (SH) and synovial PD signal were scored from 0-3 at each joint. Global indices for SH and PD signal were calculated for the 44-joint and different joint combination models for each patient. RESULTS: SH was detected in 87.8% of patients with a DAS28 <2.6 and in 81.8% of patients with an SDAI <3.3. Synovial PD signal was detected in 46.3% of patients with a DAS28 <2.6 and in 36.4% of patients with an SDAI <3.3. Wrist, second through fifth metacarpophalangeal (MCP), ankle, and second through fifth metatarsophalangeal (MTP) joint and 12-joint US assessments showed the highest correlations with the comprehensive US assessment. The wrist, MCP, ankle, and MTP joint US assessment showed the highest sensitivity for detecting SH and synovial PD signal in patients in remission according to the DAS28 and SDAI as compared to the comprehensive US assessment. CONCLUSION: US assessment of the wrist, MCP, ankle, and MTP joints can be highly sensitive for detecting residual B-mode and Doppler joint inflammation in RA patients.
23478907 Giant iliopectineal bursitis presenting as neuropathy and severe edema of the lower limb: 2013 May We report a 61-year-old woman with rheumatoid arthritis (RA: Steinblocker stage III, class 3) who developed severe swelling and neuropathy of the right lower limb caused by an iliopectineal bursa associated with destruction of the hip joint. Physical examination revealed an inguinal mass and groin pain. X-ray examination indicated destruction of the hip joint. Contrast-enhanced computed tomography showed the bursa connected with the hip joint and a markedly compressed external iliac vein among the inguinal ligament, pubis, and bursa. The patient underwent partial synovial resection and total hip arthroplasty for recovery of hip function, and this led to successful resolution of the symptoms and bursa. We present the characteristic images from this case and review all previously reported cases of RA iliopsoas bursitis causing leg swelling or neuropathy, and summarize the background. Since this lesion may cause various symptoms, clinical awareness that iliopsoas bursitis may present with unique clinical symptoms may aid correct diagnosis.
24938441 Use of DXA-based technology for detection and assessment of risk of vertebral fracture in 2014 Aug Measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) is the recommended method for diagnosis of osteoporosis and assessment of future fracture risk. However, most patients who will suffer fractures do not have osteoporosis by DXA (T-score of -2.5 or less). Bone strength, which is most closely associated with resistance to fracture, is a composite of both bone density and bone quality, and the latter is not measured by DXA. Thus, other technology is needed for non-invasive and inexpensive assessment of bone strength and fracture risk. Vertebral fractures, the most common clinical fracture in the general population, are of even greater importance in rheumatoid arthritis and other rheumatic disorders. Vertebral fracture assessment (VFA) and trabecular bone scores (TBS), two techniques which can aid prediction of future fracture risk, can be used with currently available DXA machines. Description of these techniques and their potential application to clinical rheumatology practice will be the focus of this paper.
23138884 Nodular progression of lentigo malignant melanoma during a treatment with tocilizumab: cau 2013 Feb Tocilizumab is an anti-interleukin (IL)-6 receptor monoclonal antibody, used since 2010 for the treatment of severe rheumatoid arthritis (RA). It is known to induce infection, similarly to other biotherapies which modulate immune response and cytokines. Few cases of malignancy, however, have as yet been reported. We describe here the case of a patient with severe RA, previously treated with prednisolone, methotrexate, leflunomide, etanercept, and rituximab, who, after 8 months of treatment with tocilizumab, developed rapidly progressive nodular melanoma on a preexisting pigmented lesion on her left cheek. Recently, another case of nodular melanoma under tocilizumab has been published. The possible causative role of tocilizumab and other immunomodulatory agents in the development of this malignancy is discussed. Based on the present case, dermatologic screening is recommended before initiation of tocilizumab.
23636655 The fibrin-derived citrullinated peptide β60-74Cit₆₀,₇₂,₇₄ bears the major AC 2014 Jun OBJECTIVES: To evaluate the proportions of rheumatoid arthritis (RA) sera containing anticitrullinated proteins autoantibodies (ACPA) reactive to α36-50Cit₃₈,₄₂ and/or β60-74Cit₆₀,₇₂,₇₄, two peptides identified as bearing the immunodominant epitopes of their major target, citrullinated fibrin. To analyse the relationships of anti-α36-50Cit₃₈,₄₂ and anti-β60-74Cit₆₀,₇₂,₇₄ autoantibodies with autoantibodies reactive to the complete citrullinated human fibrinogen molecule (AhFibA) and with anti-CCP2 antibodies. METHODS: 617 sera from 181 patients with established RA and 436 with non-RA rheumatic diseases were tested by ELISA for AhFibA, anti-CCP2, anti-α36-50Cit₃₈,₄₂, anti-β60-74Cit₆₀,₇₂,₇₄ autoantibodies, and by nephelometry for rheumatoid factor (RF). Diagnostic indexes, correlations and concordances between tests were analysed. Crossreactivity of anti-α36-50Cit₃₈,₄₂ and anti-β60-74Cit₆₀,₇₂,₇₄ autoantibodies was assessed in competition experiments. RESULTS: At a diagnostic specificity of 95%, the diagnostic sensitivity of AhFibA (83%) was significantly higher than that of all other tests. The diagnostic sensitivity of anti-β60-74Cit₆₀,₇₂,₇₄ (71%) was significantly higher than that of anti-α36-50Cit₃₈,₄₂ autoantibodies (51%) but similar to that of anti-CCP2 (74%). Titres of RF, anti-α36-50Cit₃₈,₄₂ and anti-β60-74Cit₆₀,₇₂,₇₄ autoantibodies were weakly correlated with each other, whereas titres of anti-β60-74Cit₆₀,₇₂,₇₄ were strongly correlated with those of AhFibA (r=0.633) and anti-CCP2 (r=0.634). Anti-α36-50Cit₃₈,₄₂ and anti-β60-74Cit₆₀,₇₂,₇₄ mainly corresponded to two non-crossreactive subfamilies of ACPA. More than 90% of AhFibA-positive or anti-CCP2-positive sera recognised the α36-50Cit₃₈,₄₂ and/or the β60-74Cit₆₀,₇₂,₇₄ peptide. CONCLUSIONS: Autoantibodies reactive to α36-50Cit₃₈,₄₂ and β60-74Cit₆₀,₇₂,₇₄ form two distinct, non-overlapping subfamilies of ACPA that, together, cover practically all the ACPA reactivity to citrullinated fibrinogen and to CCP2 antigens. In established RA, anti-β60-74Cit₆₀,₇₂,₇₄ autoantibodies show diagnostic indexes similar to those of anti-CCP2.
23836086 A rapid assay for on-site monitoring of infliximab trough levels: a feasibility study. 2013 Sep Monitoring levels of biologicals against tumor necrosis factor (TNF) has been suggested to improve therapeutic outcomes in inflammatory bowel diseases (IBDs). This pilot study describes a rapid lateral flow (LF)-based assay for on-site monitoring of serum trough levels of humanized monoclonal antibody infliximab (IFX). The applied chromatographic method utilizes sequential flows of diluted serum, wash buffer, and an immunoglobulin generic label on LF strips with a Test line comprised of TNF-α. The successive flows permitted enrichment of IFX at the Test line before the label was applied. The label, luminescent upconverting phosphor (UCP) particles coated with protein-A, emits a 550-nm visible light upon excitation with 980-nm infrared light. IFX concentrations were determined through measurement of UCP fluorescence at the Test line. The assay was optimized to detect IFX levels as low as 0.17 μg/mL in serum. For patients with IBD, this limit is appropriate to detect levels associated with loss of response (0.5 μg IFX/mL). The assay was evaluated with clinical samples from patients with Crohn's disease and correlated well within the physiologically relevant range from 0.17 to 10 μg/mL with an IFX-specific ELISA. Performance of the assay was further successfully validated with samples from blood donors, IFX negative IBD patients, and rheumatoid arthritis patients that had developed anti-IFX antibodies. Because of its generic nature, the assay is suited for detecting most therapeutic anti-TNF-α monoclonal antibodies.