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ID PMID Title PublicationDate abstract
21038107 Atlanto-axial joint of atlanto-axial subluxation patients due to rheumatoid arthritis befo 2011 May This study investigated the preoperative morphology and postoperative fusion of the atlanto-axial joint (AAJ) in patients with atlanto-axial subluxation (AAS) due to rheumatoid arthritis (RA) using computed tomography (CT). Furthermore, we examined the relationship between the preoperative morphology of AAJ and other radiographic results. Thirty patients with AAS due to RA treated by C1-2 transarticular screw fixation (TSF) were reviewed. The morphology of the AAJ was evaluated using sagittal reconstruction views on CT before and 1 year after surgery. Thereafter, the atlanto-dental interval (ADI) value at the neutral and maximal flexion position and atlanto-axial angle (AAA) at the neutral position was assessed in preoperative lateral cervical radiographs. The preoperative morphology of the AAJ on CT reconstruction views was graded as follows: Grade 1 showed maintenance of the joint space, Grade 2 showed the joint space narrowing and Grade 3 showed the destructive abnormality of subchondral bone. After surgery, the ADI value at the neutral position was assessed in lateral cervical radiographs. Furthermore, the fusion in the AAJ was investigated using CT sagittal reconstruction views taken 1 year after surgery. The preoperative CT image of the AAJ demonstrated Grade 1 in 12 cases (Group A), Grade 2 in 9 cases (Group B) and Grade 3 in 9 cases (Group C). There was no significant difference in age, gender and duration of RA among the three groups. The average ADI value at the flexion position was 11.0 mm in Group A, 12.3 mm in Group B and 12.7 mm in Group C (p>0.313). The average ADI value at the neutral position before surgery was 4.5 mm in Group A, 7.3 mm in Group B and 11.4 mm in Group C (p<0.003). The mean AAA value was 20.8° in Group A, 21.8° in Group B and 8.4° in Group C (p<0.033). The average ADI value after TSF was 1.7 mm in Group A, 2.1 mm in Group B and 3.0 mm in Group C (p>0.144). Fusion in the AAJ 1 year after surgery was demonstrated in 14 cases (46.7%; Group A, 0 case; Group B, 5 cases; Group C, 9 cases). According to the preoperative grading of the AAJ, the postoperative fusion in the AAJ was demonstrated in 0 of 32 joints (0%) in Grade 1, 7 of 18 joints (38.9%) in Grade 2 and all of 10 joints (100%) in Grade 3. In conclusion, this study showed that a destructive abnormality of subchondral bone in the AAJ induced an enlargement of the ADI and anterior inclination of the atlas in patients with AAS due to RA. The current study also showed that fusion in the AAJ was demonstrated in 14 of 30 patients after C1/2 TSF. This was easy to recognize in AAS patients whose joint destruction extended to the subchondral bone.
21558619 The pharmacokinetics of ¹²⁴I-rituximab in patients with rheumatoid arthritis. 2011 Rheumatoid arthritis is a destructive inflammatory joint disorder. Pre- and mature B-cells, characterized by CD20 antigen expression, play an important role in the inflammatory process. Rituximab, a chimeric monoclonal antibody against the CD20 antigen, has been approved since 2006 for the treatment of patients with rheumatoid arthritis. However, not all patients benefit from this treatment. Persistent activity of the disease has been reported despite treatment with rituximab. Imaging of radiolabeled rituximab can be used to monitor the biodistribution of rituximab, and potentially to predict the efficacy of the treatment. In this study, rituximab was radiolabeled with ¹²⁴Iodine for positron emission tomography (PET) imaging. The aim of this study was to investigate the pharmacokinetics and biodistribution of ¹²⁴I-rituximab in patients with rheumatoid arthritis, to establish the optimal procedure for PET imaging. Eligible patients received 50 MBq ¹²⁴I-rituximab, corresponding to approximately 1.5 mg rituximab. Wholebody PET/CT imaging was performed at 10 min, 24 hrs, and 48 hrs post injection. The total body activity, radioactivity in whole blood, and rituximab serum levels were determined. ¹²⁴I-rituximab has favorable pharmacokinetics for targeting of (pathological) B cells and imaging over several days, but only after pre-treatment with unlabeled rituximab. In addition, protection of the thyroid is recommended to prevent uptake of released ¹²⁴I.
21502422 Enzyme-linked immunosorbent assay screening then indirect immunofluorescence confirmation 2011 May The purpose of this study was to analyze antinuclear antibody (ANA) screening by enzyme-linked immunosorbent assay (ELISA) followed by indirect fluorescent antibody (IFA) testing to confirm and characterize the pattern and titer of the antibody. We evaluated 4 ANA ELISAs and 1 HEp-2 IFA substrate in 224 clinically defined serum samples consisting of 30 from systemic lupus erythematosus (SLE) cases, 94 from rheumatoid arthritis cases, and 100 from healthy donors plus 495 serum samples submitted for routine ANA testing and 12 reference serum samples distributed by the Centers for Disease Control and Prevention. IFA tests were read independently by 2 certified medical technologists. ELISA sensitivities ranged from 90% to 97% compared with 80% by IFA in the SLE serum samples. The ELISAs had specificities of 36% to 94%, whereas the IFA had 99% specificity. Overall, ELISAs for ANA assays demonstrated better sensitivity and good specificity, suggesting ELISA is a more cost-effective alternative to IFA testing for initial ANA screening. Samples positive by ANA ELISA should be tested on HEp-2 to determine the titer and pattern.
22301373 Is serum anti-cyclic citrullinated peptide level useful in the diagnosis of rheumatoid art 2012 Apr 11 BACKGROUND: To find out whether serum level of anti-cyclic citrullinated peptides (anti-CCP) could be useful in the diagnosis of rheumatoid arthritis (RA). METHODS: The study was performed against 1972 patients who visited Hanyang University Medical Center and were tested positive for anti-CCP. RESULTS: When test results were classified into 6 groups according to the anti-CCP level, diagnostic rates of RA in each group were distributed from 73.6% to 77.2%. The increase of serum level did not have any correlation with the diagnostic rate of RA. CONCLUSIONS: The level of serum anti-CCP was not useful in the diagnosis of RA.
22269659 Splinting and hand exercise for three common hand deformities in rheumatoid arthritis: a c 2012 Mar PURPOSE OF REVIEW: Hand deformities (ulnar drift, swan neck and boutonniere) are prevalent in rheumatoid arthritis and develop early in the disease process. These deformities cause significant functional impairment and impact quality of life. This review will provide a clinical perspective using the most recent evidence regarding the role of splinting and hand exercise in their management. The pathomechanics and functional consequences of these deformities are also described. RECENT FINDINGS: Patients tend to under-report their hand problems and are often reluctant to seek treatment for their deformities. There is limited evidence to support or refute the role of splinting and hand exercises in their management. Clinical experience suggests splinting and hand exercise are most beneficial when prescribed for early, flexible deformities. SUMMARY: More research is required to guide clinicians on the most effective approach to the management of these three hand deformities. It is imperative that clinicians assess for and recognize these deformities in order to ensure timely and appropriate treatment. Until more evidence becomes available, an evidenced-informed approach is recommended.
23269079 Successful treatment of immunodeficiency-associated EBV-negative lymphoproliferative disor 2012 Immunodeficiency-associated lymphoproliferative disorders (LPD) in rheumatoid arthritis are a rare, aggressive, and life-threatening clinical entity. We describe a 60-year-old man who had rheumatoid arthritis that was treated with methotrexate. Eight months after the treatment, the case was diagnosed as Epstein-Barr virus-negative LPD (diffuse large B-cell lymphoma) with abdominal bulky mass and clinical stage IVB at high risk in the international prognostic index. Immediate withdrawal of methotrexate led the patient to achieve complete remission, and 8 subsequent courses of rituximab treatment for the prevention of relapse kept the patient disease-free for 29 months. Our case suggests that these treatments may be an effective, safe, and feasible strategy for immunodeficiency-associated LPD in rheumatoid arthritis.
21952997 Correlation of fatigue with pain and disability in rheumatoid arthritis and osteoarthritis 2011 Sep OBJECTIVE: To investigate the correlation of fatigue with pain in rheumatoid arthritis patients and with disability in osteoarthritis patients. METHODS: Twenty patients with rheumatoid arthritis and 20 patients with osteoarthritis were evaluated. The degree of fatigue was evaluated with a visual analogue scale and the Multidimensional Assessment of Fatigue. Pain was evaluated with a visual analogue scale as well as Patient Global Assessment. For disability evaluation, the Health Assessment Questionnaire was performed. Age, gender, disease duration, education, income, antirheumatic drugs used and comorbidity were also obtained. Statistical analysis included Fisher exact, Shapiro-Wilk, Kruskal-Wallis and Spearman tests. The significance level was 0.05. RESULTS: Fatigue was more significantly increased in patients with osteoarthritis than in patients with rheumatoid arthritis when evaluated with Multidimensional Assessment of Fatigue (P < 0.05). Pain was found to correlate with fatigue evaluated with visual analogue scale or Multidimensional Assessment of Fatigue in patients with rheumatoid arthritis (r = 0.46; P < 0.05). Health Assessment Questionnaire was associated with fatigue visual analogue scale in patients with osteoarthritis (r = 0.54; P < 0.05). Patient Global Assessment correlates with fatigue visual analogue scale (r = 0.44; P < 0.003). Patients were similar in both groups: all females, similar mean age, with long disease duration and low income. CONCLUSION: Our results corroborate that fatigue in rheumatoid arthritis patients correlates with the degree of pain, while in osteoarthritis patients it is associated with disability. Therefore, we found that fatigue has different correlates in osteoarthritis and rheumatoid arthritis, and we suggest that disability, not pain, is a correlate of fatigue in osteoarthritis patients.
22589258 Carotid atherosclerosis, disease measures, oxidized low-density lipoproteins, and atheropr 2012 Jun OBJECTIVE: Although an enhanced risk of cardiovascular disease (CVD) in persons with rheumatoid arthritis (RA) is well established, the mechanisms behind it remain unclear. We studied whether carotid atherosclerosis, RA disease measures, or potential cardiovascular biomarkers influenced the incidence of CVD in an RA inception cohort. METHODS: RA disease measures and CVD biomarkers were assessed at 0, 3, 12, 24, and 60 months after disease onset, and carotid ultrasonography after 5 years. The study outcome was incident CVD events - acute myocardial infarction, angina pectoris, congestive heart failure, or ischemic cerebrovascular event. Survival analysis and Cox and longitudinal regressions were used for statistical analyses. RESULTS: A total of 105 patients, without CVD events prior to RA onset, experienced 17 CVD events, an incidence rate of 1.35 events per 100 person-years (95% CI 0.71-2.0). The rate of CVD events did not differ with regard to measures of carotid intima-media thickness, but it was higher for patients with bilateral carotid plaques than for those without (p = 0.012). Improvement in Disease Activity Score for 28 joints, visual analog scale for pain, and Stanford Health Assessment Questionnaire score over the first year, as well as usage of methotrexate (MTX), was associated, independent of age, with reduction of risk of CVD event [hazard ratios 0.68 (95% CI 0.5-0.97), 0.97 (95% CI 0.95-0.99), 0.35 (95% CI 0.15-0.82), and 0.34 (95% CI 0.12-0.91), respectively]. In longitudinal analyses, increasing oxidized low-density lipoprotein (oxLDL) and probability for low antiphosphorylcholine antibodies (anti-PC) were observed in those who experienced a subsequent CVD event. CONCLUSION: Bilateral carotid plaques were associated with poor CVD-free survival. Early reductions of inflammation, pain, and disability as well as MTX usage were associated with better CVD outcome. Elevated oxLDL and low IgM anti-PC levels may link chronic inflammation in RA to enhanced risk of CVD events.
21993917 Tocilizumab-induced hyperbilirubinemia in Japanese patients with rheumatoid arthritis: its 2012 Aug This study was performed to explore the possibility of an association between polymorphisms within the uridine diphosphate glucuronosyltransferase 1A1 gene (UGT1A1) and hyperbilirubinemia arising during tocilizumab therapy. We examined the distributions of 3 variant alleles, UGT1A1*6, *28, and *27, in 46 Japanese patients with rheumatoid arthritis (RA) who had received tocilizumab therapy for at least 24 weeks, grouped the patients according to their carriage status of these UGT1A1 variants, and determined the frequency of hyperbilirubinemia in each of the groups. Of the 46 patients treated with tocilizumab, 34 maintained normal bilirubin levels after 24 weeks, whereas the remaining 12 developed mild or moderate hyperbilirubinemia. Patients carrying 2 copies of UGT1A1*28 (*28/*28) were more likely to develop hyperbilirubinemia than those without UGT1A1*28. In addition, patients carrying 2 copies of variant alleles, either as homozygotes (UGT1A1*6/*6 or *28/*28) or as compound heterozygotes (UGT1A1*6/*28), were at higher risk of hyperbilirubinemia as compared with those without either UGT1A1*6 or UGT1A1*28 (odds ratio [OR] 28.33; 95% confidence interval [CI] 2.39-336.00; p = 0.005). Multivariate logistic regression analysis confirmed the strong association of tocilizumab-induced hyperbilirubinemia with the presence of 2 copies of variant alleles (OR 25.51; 95% CI 2.35-276.53; p = 0.008), yielding an area under the receiver operating characteristics curve of 0.78 (95% CI 0.60-0.95, p = 0.005). Tocilizumab can induce hyperbilirubinemia in RA patients, especially those carrying UGT1A1*6/*6, *6/*28, and *28/*28 genotypes. Considering this genetic association, it may be unnecessary to withdraw this drug from RA patients in the absence of other signs of hepatic injury. Given that tocilizumab has the potential to inhibit UGT1A1-mediated glucuronidation, however, it may inhibit not only bilirubin metabolism but also UGT1A1-dependent detoxification of drugs, thereby increasing the risk of unwanted adverse events during RA therapy.
22944142 Of bugs and joints: the relationship between infection and joints. 2013 Jul The association between microbes and joints has existed since antiquity, and remains complex. Diagnosis is often times difficult to determine despite highly suspicious clinical characteristics for the presence of an underlying infection. Over the several past decades, considerable advances have occurred in diagnostic methodologies and therapy. However, the morbidity and mortality of septic arthritis remains high. Great advances have occurred in the diagnosis, pathogenesis, and therapeutic management of reactive arthritis, and there is evidence that when the responsible microorganism is Chlamydia trachomathis, complete remission and cure is possible. Emergent infections, especially viral, has been recognized, i.e. HIV, hepatitis C, and most recently Chikengunya virus, and in the case of HIV associated articular manifestations, the introduction of HAART has resulted in a decrease in the incidence and development of newer complications such as the immune reconstitution syndrome. The infectious etiology of rheumatoid arthritis is being strongly considered once again, and the exciting association with periodontal disease is at the forefront of intense research. The gut microbiota is also being investigated and new and most interesting data is being gathered of the potential role of commensal gut organisms and the pathogenesis of rheumatoid arthritis.
21733420 First ray resection arthroplasty versus arthrodesis in the treatment of the rheumatoid foo 2011 Jun BACKGROUND: Different options exist for the operative treatment of forefoot problems and deformities in rheumatoid arthritis (RA). The current study compared first ray and resection arthroplasty with respect to patient satisfaction, clinical and functional outcome. MATERIALS AND METHODS: In a retrospective study 53 RA patients were investigated with a minimum followup of 2 years after corrective forefoot surgery. Two patient groups were distinguished: One group had been treated with arthrodesis of the first metatarsophalangeal (MTP) joint whereas the other group had been treated with a first ray resection arthroplasty. Both groups underwent resection arthroplasty at the lesser metatarsal heads. Our arthrodesis patients were significantly younger than patients with resection arthroplasty. Five patients had been treated bilaterally so that the results of 58 feet were analyzed. RESULTS: Patient satisfaction was lower in the arthrodesis group as compared to the resection arthroplasty patients. However, the arthrodesis patients revealed better functional results and showed a push-off from the hallux. No significant radiographic difference was seen in the mean hallux valgus angles. Younger patients revealed a higher disease activity and a worse general health status than older patients. Pedobarographic results demonstrated significant differences in selected foot regions, predominantly in the hallux. Peak pressures were significantly higher in the lateral midfoot and the hallux after arthrodesis as compared to the resection arthroplasty group. CONCLUSION: Patients with arthrodesis revealed better foot function during the dynamic roll-over process even though the resection arthroplasty patients were subjectively more satisfied.
21484772 Bone edema on magnetic resonance imaging is an independent predictor of rheumatoid arthrit 2011 Aug OBJECTIVE: To study magnetic resonance imaging (MRI) as a tool for early diagnosis of rheumatoid arthritis (RA) in patients with early undifferentiated arthritis (UA). METHODS: Patients (n = 116) without a specific rheumatologic diagnosis, but with ≥2 tender joints and/or ≥2 swollen joints among the metacarpophalangeal, proximal interphalangeal, wrist, or metatarsophalangeal (MTP) joints for >6 weeks but <24 months, underwent clinical, biochemical, conventional radiographic, and MRI examinations and were followed up for >12 months for the final diagnosis of RA or non-RA. Based on univariate analyses, clinical, biochemical, and imaging parameters were selected for inclusion as explanatory variables in multiple logistic regression analysis, with development of RA as the dependent variable. A prediction model was developed, and its performance was tested and compared with that of a previous model developed by van der Helm-van Mil et al (the vdHvM model). RESULTS: Of the 116 patients with early UA, 27 (23.3%) developed RA. When the prediction model was applied, which included as explanatory variables presence of hand arthritis, positivity for rheumatoid factor (RF), morning stiffness lasting >1 hour, and the Outcome Measures in Rheumatology Clinical Trials MRI summary score for bone edema in the MTP and wrist joints, the outcome of RA or non-RA was correctly identified in 82% of the patients (sensitivity 81%, specificity 82%). Another cutoff value for the prediction index in the model would allow a higher specificity (98%) and higher accuracy (83%), but lower sensitivity (36%). With the vdHvM model, RA/non-RA was predicted in 60.2% of the population. CONCLUSION: MRI evidence of bone edema in the MTP and wrist joints is an independent predictor of future RA in patients with early UA. A prediction model that includes the variables clinical hand arthritis, morning stiffness, positivity for RF, and bone edema on MRI in the MTP and wrist joints correctly identified the development or lack of development of RA in 82% of patients.
22455933 Usage of skin care products and risk of rheumatoid arthritis: results from the Swedish EIR 2012 Feb 28 INTRODUCTION: The aim of this study was to investigate the association between exposure to cosmetics, often containing mineral oil, and the risk of developing rheumatoid arthritis (RA). The study was performed against the background that occupational exposure to mineral oil has recently been shown to be associated with an increased risk for RA in man, and that injection of or percutaneous exposure to mineral-oil-containing cosmetics can induce arthritis in certain rat strains. METHODS: A population-based case-control study of incident cases of RA was performed among the population aged 18 to 70 years in a defined area of Sweden during May 1996 to December 2003. A case was defined as an individual from the study base, who received for the first time a diagnosis of RA according to the 1987 American College of Rheumatology criteria. Controls were randomly selected from the study base with consideration taken for age, gender and residential area. Cases (n = 1,419) and controls (n = 1,674) answered an extensive questionnaire regarding environmental and lifestyle factors including habits of cosmetic usage. The relative risk of developing RA was calculated for subjects with different cosmetic usage compared with subjects with low or no usage. Analysis was also performed stratifying the cases for presence/absence of rheumatoid factor and antibodies to citrulline-containing peptides. RESULTS: The relative risks of developing RA associated with use of cosmetics were all close to one, both for women and men, for different exposure categories, and in relation to different subgroups of RA. CONCLUSION: This study does not support the hypothesis that ordinary usage of common cosmetics as body lotions, skin creams, and ointments, often containing mineral oil, increase the risk for RA in the population in general. We cannot exclude, however, that these cosmetics can contribute to arthritis in individuals carrying certain genotypes or simultaneously being exposed to other arthritis-inducing environmental agents.
22648080 Magnetic resonance imaging of inflammatory arthropathies of peripheral joints. 2011 Apr As the treatment of inflammatory arthropathies has advanced with new therapies that can slow or even halt the development of disabling disease, early and accurate diagnosis has become imperative. Magnetic resonance (MR) imaging has proved to be very sensitive in the detection of erosions, but more importantly, it can demonstrate pre-erosive changes. Detection of synovitis and edema-like bone marrow lesions for initial diagnosis and as an indicator of disease progression can provide crucial information leading to therapeutic interventions before permanent joint damage occurs. Understanding the characteristic intra-articular and extra-articular MR imaging findings of the inflammatory arthritides allows the radiologist to provide appropriate consultations in the care of these patients. The MR appearances of both intra-articular and extra-articular findings of inflammatory arthritis are presented. Despite the advances in imaging, however, many of the MR findings remain nonspecific, and radiologists must avoid overdiagnosis by synthesizing all of the clinical information available into their interpretations.
22290453 [Radiological imaging in early diagnosis of rheumatoid arthritis. The role of ultrasound a 2012 Feb CLINICAL/METHODICAL ISSUE: For optimal therapy management of patients with rheumatoid arthritis (RA) specific and sensitive diagnostic methods are essential for assessment of disease activity. STANDARD RADIOLOGICAL METHODS: In addition to projection radiography, imaging techniques, in particular magnetic resonance imaging (MRI) and ultrasound (US) are becoming increasingly more important for the early diagnosis of RA. PRACTICAL RECOMMENDATIONS: The MRI and US techniques play a key role in the early imaging diagnostics of RA. Measurement of inflammation activity represents the basis of therapeutic decision-making and can be quantitatively and qualitatively determined with MRI and US. Synovitis and bone marrow edema are predictors of erosion.
21296603 Improvements in participation in usual daily activities in patients with rheumatoid arthri 2011 Mar OBJECTIVE: To examine changes in activity participation following abatacept treatment for rheumatoid arthritis (RA), and which factors contributed to such changes. METHODS: Data were analyzed from the Abatacept in Inadequate responders to Methotrexate (AIM) and Abatacept Trial in Treatment of Anti-TNF INadequate responders (ATTAIN) clinical trials of abatacept in patients with RA. Activity participation was evaluated by the validated Activity Participation Questionnaire (APaQ), along with measures of clinical response and health-related quality of life. Changes in the APaQ during the two study periods were compared between treatment groups. Multiple regression analyses were performed to investigate the determinants of change in activity participation. The relationship between clinical efficacy measures (including low disease activity state [LDAS], Disease Activity Score 28-defined remission, and European League Against Rheumatism [EULAR] responses) and changes in activity participation were investigated. RESULTS: Statistically significant, substantive improvements in activity participation were observed over the entire study period in patients treated with abatacept. Abatacept-treated patients showed improvements from baseline of 8.4 and 7.3 days in activity participation, compared with 4.5 and 1.4 days in the placebo group (P < 0.005 vs. placebo in both trials), at the end of AIM and ATTAIN, respectively. The Short Form-36 physical and mental component scores, patient global assessment, and the Health Assessment Questionnaire-Disability Index score were found to be the strongest determinants of changes in activity participation. Patients who achieved LDAS, disease remission and good EULAR responses experienced greater improvements in activity participation measures. CONCLUSIONS: Abatacept treatment substantively and significantly improved patients' ability to participate in their usual activities. The gain in activity was closely related to improvements in clinical status, physical function and quality of life.
21569598 Rheumatoid arthritis mimicking metastatic squamous cell carcinoma. 2011 May 14 We report a case of a cervical rheumatoid nodule in close relation to the hyoid bone mimicking a metastatic carcinoma. A 74-year-old female with a 15-year history of rheumatoid arthritis (RA) on treatment with methotrexate presented with tenderness of the right base of tongue. Imaging demonstrated a 1.4 cm cystic lesion at the hyoid bone. Biopsies were unsuccessful and the patient required surgical resection of the mass. A trans-cervical approach was used. Pathology revealed a necrotizing granuloma compatible with rheumatoid etiology. The clinician should be aware that, in a patient with a neck mass, in the presence of active RA, rheumatoid nodules should be part of the differential diagnosis.
21484291 A case report of a patient with rheumatoid arthritis complicated with Mycobacterium avium 2011 Dec A female patient with rheumatoid arthritis (RA) suffered from Mycobacterium avium (M. avium) infection during tocilizumab treatment. Tocilizumab was discontinued and she was treated with a recommended chemotherapy, resulting in improvement of M. avium. Tocilizumab retreatment did not aggravate M. avium infection, and radiographic abnormalities improved over 1 year after cessation of the recommended therapy. Tocilizumab may be one candidate for intractable RA patients with M. avium if any biologic is required.
22472805 Effect of biological agents on cervical spine lesions in rheumatoid arthritis. 2012 Sep 15 STUDY DESIGN: A retrospective cohort analysis. OBJECTIVE: To determine the effect of biological agents (BAs) on the development and progression of cervical spine lesions and identify predictors of lesion progression. SUMMARY OF BACKGROUND DATA: The introduction of BAs has facilitated advances in the treatment of rheumatoid arthritis (RA). BAs reduce disease activity and limit structural joint damage. However, the effect of BAs on cervical spine lesions remains unclear. METHODS: Thirty-eight subjects who received more than 2 years of continuous BA treatment were enrolled. The mean x-ray interval was 4.4 years. RA activity was evaluated by disease activity score (DAS)-C reactive protein (CRP) and matrix metalloproteinase (MMP)-3. Radiographical definitions of cervical lesions were atlanto-dental interval (ADI) more than 3 mm for atlanto-axial subluxation (AAS), Ranawat value less than 13 mm for vertical subluxation (VS), and anterior or posterior listhesis more than 2 mm for subaxial subluxation (SS). Definitions of radiographical progression were an increase of ADI more than 2 mm for AAS, a decrease of both Ranawat and Redlund-Johnell values more than 2 mm for VS, and an increase of listhesis more than 2 mm for SS. RESULTS: RA activity responded dramatically to BA therapy (DAS-CRP from 4.3 to 2.3, P < 0.01; MMP-3 from 207.9 ng/mL to 105.6 ng/mL, P < 0.01). Baseline radiographical evaluation showed no pre-existing cervical spine lesions in 12 cases, AAS in 15 cases, and VS in 11 cases. Radiological progression was found in 1 (8%) patient in the no lesion group, 12 patients (80%) in the AAS group, and 9 patients (80%) in the VS group. The incidence of progression was significantly lower in the no lesion group compared with the other groups. Multivariate regression analysis showed that the presence of pre-existing cervical lesions was the single greatest predictor of progression. CONCLUSION: BAs prevented the development of de novo cervical spine lesions in patients with RA, but failed to inhibit progression of pre-existing RA lesions.
20937307 Global DNA methylation, DNMT1, and MBD2 in patients with rheumatoid arthritis. 2011 Mar 30 OBJECTIVES: To investigate the associations of DNA methylation levels and mRNA expressions of DNA cytosine-5-methyltransferase 1 (DNMT1) and methyl CpG-binding domain 2 (MBD2) with rheumatoid arthritis (RA). METHODS: The global methylation status of DNA was measured in 65 patients with RA and 64 healthy controls by the ELISA method. DNMT1 and MBD2 mRNA were also detected in 177 RA patients and 95 controls using the quantitative real-time polymerase chain reaction method. RESULTS: The global methylation of DNA was significantly decreased in the RA patients compared to the controls (p=0.005, 95% CI=0.0835-0.4503). The patients with RA had higher expressions of DNMT1 and MBD2 mRNA than the controls (p<0.001, 95% CI=-0.0024 to -0.0053 and p<0.001, 95% CI=-0.0079 to -0.0167, respectively). We also found that the MBD2 mRNA level was not related to the disease activity of RA. However, the expression of DNMT1 mRNA tended to be associated with the disease activity of RA (p=0.08). The levels of DNA methylation and DNMT1 mRNA were significantly decreased in the patients with anti-CCP antibody compared with those without (p=0.005, 95% CI=-0.7333 to -0.1373 and p=0.003, 95% CI=-0.0071 to -0.0022, respectively). The differences in the methylation level and expressions of DNMT1 and MBD2 were not significant between the patients treated with and without anti-TNFα biological agents (Enbrel or Humira). CONCLUSION: This study demonstrated that the RA patients have a significantly lower level of DNA methylation than the controls. Moreover, RA patients have higher expressions of DNMT1 and MBD2 mRNA. The anti-TNFα biological agents do not seem to affect DNA methylation and mRNA expressions of DNMT1 and MBD2 in RA patients.