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ID PMID Title PublicationDate abstract
20713278 Instrumented Bone Preserving elbow prosthesis in rheumatoid arthritis: 2-8 year follow-up. 2010 Sep BACKGROUND: The aim of this study was to analyze the clinical and radiological results of elbow arthroplasty using the instrumented Bone Preserving (iBP) elbow prosthesis, which is the 6(th) iteration of the Kudo prosthesis, in patients with rheumatoid arthritis. METHODS: From December 1999 to August 2006, 20 total elbow replacements in 19 patients with rheumatoid arthritis were performed by 2 surgeons using the iBP. The humeral component is uncemented and the ulnar component cemented. There were 14 women and 5 men. The period of follow-up was 2-8 years, with a mean of 49 months. The mean age at time of operation was 62 years (range, 32-80). The Larsen grade and The Mayo Elbow Performance Score were used. Possible radiolucent lines or displacement of the components were evaluated yearly. RESULTS: The preoperative radiographs showed that all of the involved elbows were in grade 3-5 with an average of 4.1. All patients had a poor elbow before operation. Two elbows were moderately unstable. Three complications occurred: 1 intraoperative fracture of the medial condyl, 1 postoperative dislocation, and 1 persistent sensory ulnar neuropathy. After surgery, at the last follow-up, 3 patients had fair results, 5 good, and 12 excellent. In 6 cases, radiographic loosening of the ulnar component was observed without any clinical symptoms; none around the humeral component. CONCLUSION: The iBP elbow prosthesis in patients with rheumatoid arthritis shows good to excellent clinical results, despite radiolucency around the cemented ulnar component in some cases.
20191472 Change of synovial vascularity in a single finger joint assessed by power doppler sonograp 2010 May OBJECTIVE: To investigate the relationship between synovial vascularity assessed by quantitative power Doppler sonography (PDS) and progression of structural bone damage in a single finger joint in patients with rheumatoid arthritis (RA). METHODS: We studied 190 metacarpophalangeal (MCP) joints and 190 proximal interphalangeal (PIP) joints of 19 patients with active RA who had initial treatment with disease-modifying antirheumatic drugs (DMARDs). Patients were examined by clinical and laboratory assessments throughout the study. Hand and foot radiography was performed at baseline and the twentieth week. Magnetic resonance imaging (MRI) was performed at baseline. PDS was performed at baseline and the eighth week. Synovial vascularity was evaluated according to both quantitative and semiquantitative methods. RESULTS: Quantitative PDS was significantly correlated with the enhancement rate of MRI in each single finger joint. Comparing quantitative synovial vascularity and radiographic change in single MCP or PIP joints, the level of vascularity at baseline showed a significant positive correlation with radiographic progression at the twentieth week. The change of vascularity in response to DMARDs, defined as the percentage change in vascularity by the eighth week from baseline, was inversely correlated with radiographic progression in each MCP joint. The quantitative PDS method was more useful than the semiquantitative method for the evaluation of synovial vascularity in a single finger joint. CONCLUSION: The change of synovial vascularity in a single finger joint determined by quantitative PDS could numerically predict its radiographic progression. Using vascularity as a guide to consider a therapeutic approach would have benefits for patients with active RA.
20609263 Central role of nitric oxide in the pathogenesis of rheumatoid arthritis and systemic lupu 2010 Nitric oxide (NO) has been shown to regulate T cell functions under physiological conditions, but overproduction of NO may contribute to T lymphocyte dysfunction. NO-dependent tissue injury has been implicated in a variety of rheumatic diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Several studies reported increased endogenous NO synthesis in both SLE and RA, and recent evidence suggests that NO contributes to T cell dysfunction in both autoimmune diseases. The depletion of intracellular glutathione may be a key factor predisposing patients with SLE to mitochondrial dysfunction, characterized by mitochondrial hyperpolarization, ATP depletion and predisposition to death by necrosis. Thus, changes in glutathione metabolism may influence the effect of increased NO production in the pathogenesis of autoimmunity.
20576092 Early combination disease-modifying antirheumatic drug therapy and tight disease control i 2010 INTRODUCTION: Early treatment of rheumatoid arthritis (RA) has been shown to retard the development of joint damage for a period of up to 5 years. The aim of this study was to evaluate the radiologic progression beyond that time in patients with early RA initially treated with a combination of three disease-modifying antirheumatic drugs (DMARDs) or a single DMARD. METHODS: A cohort of 199 patients with early active RA were initially randomized to receive treatment with a combination of methotrexate, sulfasalazine, and hydroxychloroquine with prednisolone (FIN-RACo), or treatment with a single DMARD (initially, sulfasalazine) with or without prednisolone (SINGLE). After 2 years, the drug-treatment strategy became unrestricted, but still targeted remission. The radiographs of hands and feet were analyzed by using the Larsen score at baseline, 2, 5, and 11 years, and the radiographs of large joints, at 11 years. RESULTS: Sixty-five patients in the FIN-RACo and 65 in the SINGLE group had radiographs of hands and feet available at baseline and at 11 years. The mean change from baseline to 11 years in Larsen score was 17 (95% CI, 12 to 26) in the FIN-RACo group and 27 (95% CI, 22 to 33) in the SINGLE group (P=0.037). In total, 87% (95% CI, 74 to 94) and 72% (95% CI, 58 to 84) of the patients in the FIN-RACo and the SINGLE treatment arms, respectively, had no erosive changes in large joints at 11 years. CONCLUSIONS: Targeting to remission with tight clinical controls results in low radiologic progression in most RA patients. Patients treated initially with a combination of DMARDs have less long-term radiologic damage than do those treated initially with DMARD monotherapy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN18445519.
20597264 [Prevalence of rheumatoid arthritis in Russia (according to epidemiological findings)]. 2010 AIM: To define the prevalence of rheumatoid arthritis (RA) from the data of an epidemiological study. SUBJECTS AND METHODS: During a questionnaire survey of 37057 adults of Russia, patients with complaints of articular swelling (n = 4975) were selected; of the latter a group (n = 3420) was randomly formed to be clinically examined by rheumatologists in order to detect RA. The 1987 ACR criteria were used for its diagnosis. RESULTS: According to the data of the questionnaire survey, RA was diagnosed in 159 (4.6%) of the 3420 patients with complaints of articular swelling. The prevalence of RA in Russia averaged 0.61%. Among the respondents who complained about articular swelling during the questionnaire survey, 258 (7.5%) respondents considered to have RA before rheumatological examination. While comparing the diagnoses reported by the respondents during the survey and the final diagnosis established by a specialist, RA was confirmed only in 61 (24%) patients. Out of all the identified patients with RA (n = 159), only 61 (38%) were aware of their diagnosis. In RA patients with less than one-year articular complaints (n = 24), 17% were familiar with their diagnosis; the diagnosis was first made in the others (n = 20). Among the patients with long-term articular complaints (n = 135), 42% were aware of their diagnosis. CONCLUSION: The epidemiological survey indicated that the number of patients with RA were twice higher than those given in the official statistics of the Russian Federation (671,000 versus 300,000, respectively). In outpatient practice, RA is correctly diagnosed only in 38% of cases. There is a significant hyperdiagnosis of this disease. The duration of articular complaints affects the establishment of the diagnosis of RA.
19950296 Contribution of a haplotype in the HLA region to anti-cyclic citrullinated peptide antibod 2009 Dec OBJECTIVE: To examine the risk of anti-cyclic citrullinated peptide (anti-CCP) antibody positivity in rheumatoid arthritis (RA) patients carrying certain haplotypes in the HLA region. METHODS: A total of 1,389 Japanese patients with RA were genotyped for 30 single-nucleotide polymorphisms (SNPs) in the HLA region using commercial oligonucleotide arrays (from Perlegen or Affymetrix) as well as for HLA-DRB1 alleles using a sequence-specific polymerase chain reaction method. Stepwise logistic regression was used to select from among the 30 SNPs the ones that represented a risk of anti-CCP antibody positivity. Haplotypes of the selected SNPs were inferred using an expectation-maximization algorithm. Associations of individual SNPs were evaluated with the Cochran-Armitage test for trend. DRB1 alleles and haplotypes were evaluated with the chi-square test. Heterogeneities of risks among the shared epitope (SE) and non-SE HLA-DRB1 alleles were examined using the exact test. Haplotype associations that were independent of individual HLA-DRB1 alleles were evaluated using the likelihood ratio test. RESULTS: Significant associations were found for 9 SNPs (smallest P value being 2.4x10(-8)) and in 4 HLA-DRB1 alleles (smallest P value being 2.0x10(-10) in DRB1*0405). Stepwise logistic regression selected 4 SNPs (rs9262638, rs7775228, rs4713580, and rs9277359). Among the 16 inferred haplotypes of these 4 SNPs, 6 indicated significant associations (smallest P value being 1.9x10(-11)). Risks among SE and non-SE alleles were significantly heterogeneous (P=0.0095 and P=9.8x10(-9), respectively), indicating the importance of stratification with individual DRB1 alleles rather than SE alleles. Conditional analysis of the risk associated with individual DRB1 alleles identified a risk haplotype that was independent of DRB1 (odds ratio 2.00 [95% confidence interval 1.44-2.79], P=2.6x10(-5)). CONCLUSION: Heterogeneous risks of anti-CCP antibody positivity were confirmed among SE and non-SE alleles in our patient population. A risk haplotype in the HLA region that is independent of HLA-DRB1 was confirmed.
19772499 [The use of atorvastatin in patients with rheumatoid arthritis with hyperlipidemia]. 2009 AIM: To assess efficacy and tolerability of atorvastatin and its lipid lowering and antiinflammatory effects as well as action on function of endothelium and elastic properties of arteries in patients with rheumatoid arthritis (RA) and hyperlipidemia. MATERIAL: Patients with RA (n=50) were divided into 2 groups. The main group comprised 30 patients receiving atorvastatin (10 mg/day) as a component of complex therapy. The group of comparison comprised 20 patients with similar clinical characteristics and baseline lipid levels. RESULTS: The use of atorvastatin in complex therapy led not only to lowering of levels of atherogenic fractions of lipids but also to substantial lowering of levels of systemic inflammation and diminishment of endothelial damage. Positive action of 6 month therapy with atorvastatin on elastic properties of arteries was demonstrated. Tolerability of atorvastatin was good. CONCLUSION: The data obtained allow to recommend the use of atorvastatin for long term management of hyperlipidemia in patients with RA.
19431075 Angiogenesis inhibitors for the treatment of chronic autoimmune inflammatory arthritis. 2009 May Angiogenesis, the formation of new blood vessels, is closely linked with both the initiation and progression of rheumatoid arthritis (RA). Rheumatoid joints contain elevated levels of proangiogenic molecules, such as VEGF, basic FGF, hypoxia-inducible factor 1 and angiopoietins. Increased angiogenesis is also associated with malignancies and proliferative retinopathies, and targeting this process therapeutically has proven beneficial in treating several of these diseases including colorectal, kidney and lung cancer. Adapting such a therapeutic strategy to the treatment of RA may prove beneficial, as data from preclinical studies have demonstrated that angiogenesis inhibitors reduce pannus formation, inflammation and joint erosion. New therapies that inhibit angiogenesis by blocking VEGFR tyrosine kinase signaling, integrin interactions, microtubule formation and endothelial cell proliferation may be applicable to the treatment of RA. There are several angiogenesis inhibitors that have been approved by the FDA or are currently being assessed in clinical trials which are safe for use in humans, although their effects on RA remain untested. This review discusses the potential of angiogenesis inhibition in the context of treating RA.
20191522 Improvement in work place and household productivity for patients with early rheumatoid ar 2010 Feb OBJECTIVE: To evaluate household and work place outcomes for patients with rheumatoid arthritis (RA) who were homemakers or employed workers, respectively, and who were treated with adalimumab plus methotrexate versus methotrexate monotherapy. We also determined baseline predictors of household and work place outcomes. METHODS: Data were from a health economic companion study to PREMIER, a 2-year, randomized controlled trial of methotrexate-naive patients with early RA (<3 years) who received treatment with adalimumab plus methotrexate, adalimumab, or methotrexate. Absenteeism (number of days missed or unfit to work), presenteeism (self-judgment of the effects of RA on job or household performance), and employment status were collected from self-reports at baseline and varying time points during the study. RESULTS: Household and work place outcomes were generally similar for homemakers and employed workers. Over 2 years, patients who received combination therapy missed approximately half as many days as patients who received methotrexate (17.4 versus 36.9 days for employed workers; 7.9 versus 18.6 days for homemakers). Presenteeism was lower (reflecting better productivity) for combination therapy than methotrexate monotherapy. The likelihood of gaining/retaining employment over 2 years was greater for combination therapy than methotrexate monotherapy (odds ratio 1.530, 95% confidence interval 1.038-2.255; P = 0.0318). Baseline radiographic progression was an independent predictor for retaining/gaining employment at 2 years. CONCLUSION: Compared with methotrexate monotherapy, combination therapy was associated with more positive work outcomes: less absenteeism, less presenteeism, and greater likelihood of gaining/retaining employment. Radiographic progression at baseline was predictive of the ability to retain or gain employment.
19187298 Multicentric reticulohistiocytosis with lungs and liver involved. 2009 Mar We describe a 56-year-old man with a 2-year history of papulonodules, pruritic and painful on palpation, on the head, trunk, limbs, buttocks and scrotum and a 1.5-year history of rheumatoid arthritis-like joint changes. Biopsies from the nodules on the head and left elbow revealed multinucleated giant cells with eosinophilic 'ground-glass' cytoplasm. Computed tomography revealed that there were scattered nodules in the liver and both lungs. Biopsies taken from nodules in the right lung and liver were consistent with multicentric reticulohistiocytosis. The widely scattered cutaneous papulonodules and the generalized systemic involvement make this patient interesting, and the condition should be differentiated from other diseases in clinicopathological practice.
18818228 A functional Ser(413)/Ser(413) PAI-2 polymorphism is associated with susceptibility and da 2009 Mar Systemic lupus erythematosus in some cases is characterized for development of thrombotic events with a significantly increased risk of mortality. The frequencies and clinical associations of Ser(413)/Cys(413) PAI-2 polymorphism in 40 systemic lupus erythematosus, 50 rheumatoid arthritis patients, and 100 healthy subjects were investigated. The Ser(413)/Ser(413) genotype frequency was 53% (lupus), 36% (rheumatoid arthritis), and 35% (healthy subjects). The Ser(413) allele was associated with systemic lupus erythematosus (P = .04, odds ratio = 1.76, 95% confidence interval = 1.01-3.06). In all, 4 patient carriers of Ser(413)/Ser(413) genotype, developed thrombotic events. The lupus patients identified with Ser( 413)/Ser(413) genotype showed an increased damage (57%), compared with Ser(413)/Cys(413) and Cys(413)/Cys(413) genotypes, with significant difference (P = .03). These findings suggest an association of Ser( 413) /Ser( 413) genotype with greater damage index score and Ser( 413) allele with systemic lupus erythematosus. Besides, PAI-2 polymorphism could be related with thrombotic phenomena in systemic lupus erythematosus.
20219786 The role of rheumatoid arthritis genetic susceptibility markers in the prediction of erosi 2011 Jan OBJECTIVES: Recent whole-genome and candidate gene association studies in RA have identified a number of single nucleotide polymorphisms (SNPs) that predispose to disease with moderate risk. It remains poorly understood how recently identified genetic factors may contribute to RA severity. We therefore sought to investigate the role of recently identified RA susceptibility SNP markers in predicting erosive outcome in patients with recent-onset inflammatory polyarthritis (IP). METHODS: DNA and X-ray data were available for 1049 patients who were registered between 1990 and 2003 with the Norfolk Arthritis Register (NOAR); a primary care-based inception cohort of patients with recent-onset IP. Demographic and clinical data were recorded at inclusion, and at yearly assessments thereafter. Patients were genotyped for 18 SNP markers. The presence of serum anti citrullinated peptide antibodies (ACPAs) was assessed in samples collected at inclusion to the NOAR. The association of serological and genetic markers with poor radiological (Larsen) score at Years 1 and 5, and erosions at Years 1 and 5 was investigated. RESULTS: Baseline ACPA positivity was associated with erosive disease and higher radiological damage. SNP markers within the TRAF1/C5 locus were associated with erosive disease at Year 1 [rs2900180: odds ratio (OR) 1.53 (95% CI 1.14, 2.05)] and Year 5 [rs2900180: OR 1.47 (95% CI 1.07, 2.02)]. None of the SNP markers tested was associated with Larsen score. CONCLUSION: Our results are in keeping with a previous report and suggest that the TRAF1/C5 region is associated with risk of development of radiological erosions in IP/RA patients. The finding requires replication in other large data sets.
19822053 Identification of similarities and differences in functioning in persons with rheumatoid a 2009 Jul OBJECTIVE: The objective of this study is to identify similarities and differences in functioning in AS and RA using the ICF as the framework for the description of functioning. METHODS: The Comprehensive ICF Core Sets for RA and AS were compared qualitatively regarding their content. A comparison study of common second-level ICF categories from both ICF Core Sets collected in two different cross-sectional studies in the Netherlands was performed. Significant differences regarding the level of impairments, limitations or restrictions were analyzed within the Mann-Whitney U-Test. To study whether the common ICF categories have different meaning for the two populations the Rasch model for dichotomous response option was used. RESULTS: The Comprehensive ICF Core Set for AS includes 74 ICF categories in 19 chapters and the Comprehensive ICF Core Set for RA includes 96 ICF categories in 22 chapters. Interviews among 87 patients with AS and 143 patients with RA on 24 of the common ICF categories revealed significant differences regarding the extent of problems. DIF analyses reflect that the meaning of some ICF categories, such as 'd410 Changing basic body positions' is different in relation to functioning depending on the health condition. CONCLUSION: This study was the first to compare functioning in AS and RA based on the ICF. The results confirmed to a large extend the experiences well known from other studies and thereby showed that the ICF is useful to describe and compare functioning. Some aspects could be identified which are not easy to understand with existing evidence and need to be explained in the future.
20017457 Serum and synovial fluid concentrations of CCL2 (MCP-1) chemokine in patients suffering rh 2009 OBJECTIVE: To determine serum and synovial fluid (SF) concentrations of monocyte chemoattractant protein-1 (MCP-1) or CCL2 chemokine, in patients suffering (RA) and osteoarthritis (OA) and to correlate the values to disease activity, and other patient- and disease-related parameters. METHODS: The CCL-2/MCP-1 chemokine (CK) was measured in serum and SF of 30 RA and 15 OA patients using specific and very sensitive ELISA assay. RESULTS: The CCL2/MCP-1 CK was found in increased amounts in SF compared to serum (p < 0.001) and in RA compared to OA patients (p < 0.001). The values were significantly greater in RA patients with more active disease. Greater mean SF concentrations were observed in older RA patients, in patients with longer duration of RA disease and in those who had been treated with methotrexate. Also positive correlation was found between RA SF concentrations and SF leukocyte numbers (r = 0.497, p < 0.05). CONCLUSIONS: The SF and serum CCL2/MCP-1 concentrations are significantly greater in RA than in OA and in hda-RA than in mda-RA; increased SF over serum concentrations suggest that CCL2/MCP-1 is mainly produced locally by activated cells where it may exacerbate and sustain inflammation by attracting proinflammatory leukocytes, predominantly monocytes (Tab. 1, Fig. 2, Ref. 50). Full Text (Free, PDF) www.bmj.sk.
22053612 Serum pentraxin 3 and interleukin-6 are associated with subclinical atherosclerosis in rec 2010 Subclinical atherosclerosis is increased in patients with rheumatoid arthritis (RA), as chronic systemic inflammation leads to accelerate atherosclerosis and increase arterial stiffness in theses patients. This study aimed to evaluate the association of serum interleukin-6 (sIL-6) and serum pentraxin 3(sPTX3) with subclinical atherosclerotic in patients with recent-onset rheumatoid arthritis. Sixty patients with recent onset RA (12-24 months) and 20 controls were investigated. Carotid ultrasound examination, assays for lipid profile, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor, sPTX3 and sIL-6 were done. RA patients demonstrated significantly higher carotid intima-media thickness (cIMT) values and increased carotid plaques than the control (P < 0.001 and P = 0.02, respectively). Levels of ESR, CRP, sPTX 3 and sIL-6 were significantly higher in RA patients than controls. RA related risk factors (disease duration, CRP, ESR, and duration of treatment with steroids), as well as sPTX 3, sIL-6 and cIMT were significantly higher in RA with atherosclerotic carotid plaques compared to those without atherosclerotic carotid plaques (all < 0.05). It is concluded that accelerated atherosclerosis in patients with recent-onset RA is associated with elevated levels of CRP, sPTX 3 and sIL-6.
19740905 Evaluation of several ultrasonography scoring systems for synovitis and comparison to clin 2010 May OBJECTIVES: To evaluate different global ultrasonographic (US) synovitis scoring systems as potential outcome measures of rheumatoid arthritis (RA) according to the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) filter. METHODS: To study selected global scoring systems, for the clinical, B mode and power Doppler techniques, the following joints were evaluated: 28 joints (28-joint Disease Activity Score (DAS28)), 20 joints (metacarpophalangeals (MCPs) + metatarsophalangeals (MTPs)) and 38 joints (28 joints + MTPs) using either a binary (yes/no) or a 0-3 grade. The study was a prospective, 4-month duration follow-up of 76 patients with RA requiring anti-tumour necrosis factor (TNF) therapy (complete follow-up data: 66 patients). Intraobserver reliability was evaluated using the intraclass correlation coefficient (ICC), construct validity was evaluated using the Cronbach alpha test and external validity was evaluated using level of correlation between scoring system and C reactive protein (CRP). Sensitivity to change was evaluated using the standardised response mean. Discriminating capacity was evaluated using the standardised mean differences in patients considered by the doctor as significantly improved or not at the end of the study. RESULTS: Different clinimetric properties of various US scoring systems were at least as good as the clinical scores with, for example, intraobserver reliability ranging from 0.61 to 0.97 versus from 0.53 to 0.82, construct validity ranging from 0.76 to 0.89 versus from 0.76 to 0.88, correlation with CRP ranging from 0.28 to 0.34 versus from 0.28 to 0.35 and sensitivity to change ranging from 0.60 to 1.21 versus from 0.96 to 1.36 for US versus clinical scoring systems, respectively. CONCLUSION: This study suggests that US evaluation of synovitis is an outcome measure at least as relevant as physical examination. Further studies are required in order to achieve optimal US scoring systems for monitoring patients with RA in clinical trials and in clinical practice.
19019893 Monitoring anti-TNFalpha treatment in rheumatoid arthritis: responsiveness of magnetic res 2009 Oct OBJECTIVES: To evaluate the responsiveness of magnetic resonance imaging (MRI) and ultrasonography (US) compared with conventional measures of disease activity and structural damage in patients with rheumatoid arthritis (RA) during the first year of treatment with anti-tumour necrosis factor alpha (TNFalpha). METHODS: A cohort of patients with RA (N = 36, median age 53 years, disease duration 7.6 years and disease activity score (DAS28) 5.7) was evaluated by core measures of disease activity, US (one wrist), MRI (one wrist) and conventional radiography (CR, both hands and wrists) at initiation of treatment with anti-TNFalpha agents and after 3, 6 and 12 months. Responsiveness was assessed by standardised response means (SRM). Accepted thresholds were applied to classify responsiveness as trivial, low, moderate or good. RESULTS: MRI synovitis (SRM between -0.79 and -0.92) and the MRI total inflammation score comprising synovitis, tenosynovitis and bone marrow oedema (SRM between -1.05 and -1.24) were highly responsive. Moderate to high responsiveness was found for MRI tenosynovitis and bone marrow oedema, all the composite indices (DAS28, simplified disease activity index (SDAI) and clinical disease activity index (CDAI)) and the 28-swollen joint count. US displayed low to moderate responsiveness. The MRI erosion score displayed low responsiveness but was more responsive than CR measures at 3 and 6 months follow-up. MRI and CR measures of annual progression rates of damage performed similarly and were highly responsive. CONCLUSIONS: The most responsive measure of inflammation when evaluating anti-TNFalpha medication was a composite measure comprising MRI synovitis, tenosynovitis and bone marrow oedema, and this may be a promising outcome measure in clinical studies.
19417117 Anaphylactic reaction to anakinra in a rheumatoid arthritis patient intolerant to multiple 2009 May OBJECTIVE: To report a case of probable anaphylaxis due to anakinra in a patient with rheumatoid arthritis and multiple drug allergies. CASE SUMMARY: A 46-year-old Indian female with rheumatoid arthritis demonstrated distinct adverse reactions to all commercially available anti-tumor necrosis factor therapies, sulfasalazine, and hydroxychloroquine. Over a 4-year period her disease remained active during therapy with methotrexate and prednisone. Biologics were added sequentially, with development of intolerable reactions, first to infliximab (urticarial rash, infusion reactions) after 3 doses, and then to etanercept (autoantibodies, worsening Raynaud's phenomenon, digital microinfarcts) after 1 year. Following 2 months of daily injections of anakinra, she experienced an immediate immunoglobulin E-mediated anaphylactic reaction within 20 minutes of an injection, as evidenced by positive testing to both anakinra and histamine with the skin prick method. The patient subsequently started adalimumab therapy, which was discontinued after the fourth dose due to the development of generalized hives. DISCUSSION: The Naranjo probability scale demonstrated a probable relationship between anaphylaxis and anakinra in this patient. Although cases of anakinra-related hypersensitivity have been reported in patients in which therapy was interrupted and then reintroduced, to our knowledge, this is the first report of anaphylaxis with continuous therapy. CONCLUSIONS: This unusual case of a patient with multiple drug allergies presents a difficult clinical scenario, which was unsuccessfully managed with multiple biologic therapies on a trial-and-error basis. In the future, pharmacogenetics may help to better identify individuals at risk for multiple drug reactions and preclude unnecessary exposure to potentially harmful therapeutic options in similar patients.
20156948 Inflammation and microvascular and macrovascular endothelial dysfunction in rheumatoid art 2010 Apr OBJECTIVE: To determine whether abnormalities in microvascular and macrovascular function in rheumatoid arthritis (RA) are associated with plasma markers [von Willebrand factor (VWF)] of endothelial dysfunction and inflammation [C-reactive protein (CRP)] and whether the abnormalities would be altered by treatment. Endothelial dysfunction and inflammation in RA may contribute to adverse cardiovascular events. Although endothelial dysfunction in RA has been demonstrated by altered plasma markers, the relationships with macrovascular and microvascular function are relatively unexplored. METHODS: We recruited 66 patients with chronic RA, 48 community controls (CC), and 25 patients with diabetes and hypertension as a disease control group (DC). Subjects had venous blood sampled for plasma markers, and underwent laser Doppler perfusion imaging of forearm skin (to assess microvascular circulation) following acetylcholine and sodium nitroprusside iontophoresis, to assess endothelium-dependent and endothelium-independent responses, respectively. Brachial artery flow-mediated dilatation assessed endothelial dysfunction in a macrovascular bed. A subgroup of 29 patients with RA were assessed pretherapy and after 2-4 weeks of antirheumatic therapy. RESULTS: As expected, patients with RA had higher CRP, erythrocyte sedimentation rate (ESR), and VWF. Endothelium-independent vasoreactivity was abnormal in RA, and this correlated negatively with CRP. All aspects of microvascular function were abnormal in the DC compared to the CC. Macrovascular function was preserved in RA but was abnormal in the DC group. Four weeks of antiinflammatory therapy reduced CRP and ESR but had no effect on any vascular function index in the patients with RA. CONCLUSION: Patients with RA have abnormal endothelium-independent microvascular function that correlates with inflammation but is not altered by short-term antiinflammatory therapy.
19559690 Lymphocyte transformation test is not helpful for the diagnosis of methotrexate-induced pn 2009 Sep BACKGROUND: The pathophysiology underlying methotrexate (MTX)-induced pneumonitis has been considered as a hypersensitive reaction. The lymphocyte transformation test (LTT) is frequently used to detect hypersensitivity. Whereas previous reports have proposed that the LTT is not ideal to detect hypersensitivity to MTX, it has not been directly confirmed. METHODS: Forty rheumatoid arthritis (RA) patients (24 patients currently taking MTX and 16 patients with a past history of MTX administration) and 13 healthy subjects were recruited. LTT with MTX was used to assess thymidine incorporation. An MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay was also performed. The mitogenic activity was expressed as the Stimulatory Index (SI). The activity of RA was assessed by the disease activity score 28 (DAS28). RESULTS: In the presence of MTX, the SI measured by the LTT and by the MTS assay showed an inverse correlation. The presence of MTX significantly elevated the SI values measured by the LTT. However, the SI values were significantly lower in RA patients currently taking MTX than those of patients not currently taking MTX, although DAS28 was not different. Furthermore, a past history of MTX-induced pneumonitis did not affect the SI values. CONCLUSION: LTT with MTX in RA patients is not appropriate to detect MTX-induced pneumonitis.