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Long-term bone mineral density (BMD) changes and the associated factors in systemic lupus erythematosus (SLE) patients were assessed. Despite the remarkably low overall bone loss, significant spine bone loss was associated with the use of glucocorticoids, use of antimalarials, and lower 25-hydroxyvitamin D levels, stressing the importance of prevention of osteoporosis and vitamin D deficiency in SLE patients. The aim of this study is to assess the BMD changes in patients with SLE and to identify the associated factors. Demographic and clinical data of 126 SLE patients were collected, and BMD measurements of the lumbar spine and the total hip were performed by dual-energy X-ray absorptiometry at baseline and follow-up. Statistical analyses were performed using independent Mann–Whitney U tests and linear regression analyses. At baseline, 39.7 % of the patients (90 % female, mean age 39 ± 12.2 years) had osteopenia, and 6.3 % had osteoporosis. The median follow-up duration was 6.7 years (range 1.9–9.3 years). Mean changes in BMD at the lumbar spine (−0.08 %/year) and the hip (−0.20 %/year) were not significant. During follow-up, 70 % of the patients used glucocorticoids. The mean ± SD daily glucocorticoid dose was 5.0 ± 5.0 mg. In multiple regression analysis, BMD loss at the spine was significantly associated with higher daily glucocorticoid dose and lower baseline 25-hydroxyvitamin D levels. BMD loss at the hip was associated with lower 25-hydroxyvitamin D levels at baseline, reduction of body mass index, and baseline use of antimalarials. In this 6-year follow-up study, bone loss was remarkably low. A dose-dependent relationship between glucocorticoid use and spinal bone loss was found. In addition, the use of antimalarials and lower 25-hydroxyvitamin D levels at baseline were associated with BMD loss. These findings underline the importance of prevention and treatment of vitamin D deficiency and osteoporosis in SLE, especially in patients using glucocorticoids or antimalarials.

Contains fulltext : 79951.pdf (Publisher’s version ) (Closed access) The aims of this study were to describe rheumatoid arthritis patients' compliance with continued exercise after participation in a 2-year supervised high-intensity exercise program and to investigate if the initially achieved effectiveness and safety were sustained. Data were gathered by follow-up of the participants who completed the 2-year high-intensity intervention in a randomized controlled trial (Rheumatoid Arthritis Patient In Training study). Eighteen months thereafter, measurements of compliance, aerobic capacity, muscle strength, functional ability, disease activity, and radiological damage of the large joints were performed. Seventy-one patients were available for follow-up at 18 months, of whom 60 (84%) were still exercising (exercise group: EG), with average similar intensity but at a lower frequency as the initial intervention. Eleven patients (16%) reported low intensity or no exercises (no-exercise group: no-EG). Patients in the EG had better aerobic fitness and functional ability, lower disease activity, and higher attendance rate after the initial 2-year intervention. At follow-up, both groups showed a deterioration of aerobic fitness and only patients in the EG were able to behold their muscle strength gains. Functional ability, gained during the previous participation in high-intensity exercises, remained stable in both groups. Importantly, no detrimental effects on disease activity or radiological damage of the large joints were found in either group. In conclusion, the majority of the patients who participated in the 24-month high-intensity exercise program continued exercising in the ensuing 18 months. In contrast to those who did not continue exercising, they were able to preserve their gains in muscle strength without increased disease activity or progression of radiological damage.

While cyclosporin has an established role in the treatment of rheumatoid arthritis there is concern about adverse effects, mainly related to renal function. With new interest being generated in cyclosporin combination therapy, and the availability of a new form of cyclosporin (cyclosporin microemulsion), focus on adverse effects and drug interactions of this compound remains important. Over the years, rheumatologists have been aware of these adverse effects and consensus meetings have resulted in guidelines for the use of cyclosporin. If these guidelines are followed, structural renal damage can be minimal. Cyclosporin should be started at a low dose and titrated against the highest acceptable increase in serum creatinine, that is, a 30% increase over the pretreatment value. At present, there is no evidence that cyclosporin in combination with other antirheumatics leads to increased toxicity. With regard to long term unwanted effects, neither the pattern nor the risk of malignancies associated with the use of cyclosporin seems to differ from other antirheumatics. The place of cyclosporin in the treatment of rheumatoid arthritis seems to be established. The most promising results will come from early rheumatoid arthritis combination studies involving cyclosporin with other antirheumatics, especially methotrexate.

Objective. Comparison of clinically observed neurologic long tract signs in a heterogeneous group of patients with rheumatoid arthritis (RA), with morphologic abnormalities of the cervical spine as depicted on radiographs and magnetic resonance (MR) images. Design. The patients were prospectively assigned to one of three classes on the basis of their neurologic status. Lateral cervical spine radiographs and sagittal T1-weighted and gradient echo images were performed. The qualitative MR features evaluated were erosion of the dens and atlas, brain stem compression, subarachnoid space encroachment, pannus around the dens, appearance of the fat body caudal to the clivus, and the signal intensity of the pannus. The quantitative imaging parameters were the cervicomedullary angle and the distance of the dens to the line of McRae. Patients. Sixty-three consecutive patients with RA and subjective symptoms, especially neck or occipital pain, and/or clinical objective signs consistent with a compromised cervical cord were included in this study. Results and conclusions. Damage documented with radiographs and MR imaging in patients with RA is often severe, even in those without neurologic signs (class 1). None of the abnormalities confined to the atlantoaxial level correlated significantly with neurologic classification. Subarachnoid space encroachment anywhere in the entire cervical spine did correlate significantly with neurologic classification.

Interest in the use of tetracyclines, especially minocycline, in arthritis is described in relation to the historical background. The scientific basis for the use of tetracyclines in rheumatoid arthritis is discussed in the light of new insights into the pathophysiology of the disease. During the past 2 years several studies have been published on the use of minocycline in rheumatoid arthritis. The results of these studies were to a large extent similar, in that minocycline was beneficial in terms of clinical outcome measures, but had more pronounced effects on laboratory assessments. Finally, we speculate about the future role of minocycline in rheumatoid arthritis.

Background In case of contraindications or intolerance during treatment with oral bisphosphonates (OB), administration of pamidronate intravenously is a widely used alternative. In this study we compared the effect on change in bone mineral density (BMD) of the spine and hip during long term treatment with pamidronate iv in comparison to OB. Methods We studied 61 patients receiving treatment for at least two years. In case of contraindications or intolerance (within 3 months) of an OB, pamidronate iv was started. BMD was measured on a Hologic 4500 and a Lunar DPX-IQ at the spine (L1-L4) and total hip. Results Thirty-one patients were enrolled in the OB group and 30 in the intravenous pamidronate group. Mean follow-up duration (SD) was 4.3 (1.3) years. We observed a significant increase (p < 0.001) in spinal BMD, both in the OB group (8.3%) as well as in the pamidronate iv group (6.1%), but no significant difference in BMD change between the OB and pamidronate iv groups. At the hips, we observed a tendency to increased BMD in both groups, 1.1% in the OB and 1.4% in the pamidronate iv group. Conclusion We conclude that intravenous pamidronate is a good alternative for oral bisphosphonates in the treatment of osteoporosis in patients with contraindications or intolerance during treatment with oral bisphosphonates.

Cardiac involvement is very common in patients with systemic lupus erythematosus since 30 to 50% of all patients suffer from some sort of heart disease (Lahita, Textbook of rheumatology, 1997). Pericarditis is the most common form of involvement and occurs in 19 to 48% of patients (Lahita, Textbook of rheumatology, 1997). Pleural and/or pericardial pain can occur in any phase of the disease; however, pericardial effusion leading to cardiac tamponade is rare (Lahita, Textbook of rheumatology, 1997; Lee et al., Journal of Korean Medical Science 12(1):75-77, 1997). We report such a case, illustrated by echocardiography.

An insertion mutation at nucleotide 3020 (3020insC) and a missense mutation G2722C in the CARD15 gene on chromosome 16p have been reported to be associated with Crohn's disease (CD). The protein encoded by the CARD15 gene is expressed in peripheral monocytes and regulates apoptosis and NF-κB activation, factors which play an important role in inflammation. Since CD and ankylosing spondylitis (AS) are interrelated disorders, we have investigated whether these mutations in the CARD 15 gene are also associated with AS. We studied 113 unrelated AS patients and 152 unrelated healthy controls. No significant differences were found between patients and controls in the prevalence of the insertion 3020insC mutation and the G2722C missense mutation, OR = 1.36, 95% CI: 0.27-6.84, P = 0.70 and OR = 0. 58; 95% CI: 0. 18-1.94; P = 0.38, respectively. We conclude that the insertion 3020insC mutation and the G2722C missense mutation in the CARD15 gene are not involved in the susceptibility to AS. © 2003 Nature Publishing Group All rights reserved.

B cell depletion therapy is efficacious in rheumatoid arthritis (RA) patients failing on tumor necrosis factor (TNF) blocking agents. However, approximately 40% to 50% of rituximab (RTX) treated RA patients have a poor response. We investigated whether baseline gene expression levels can discriminate between clinical non-responders and responders to RTX. In 14 consecutive RA patients starting on RTX (test cohort), gene expression profiling on whole peripheral blood RNA was performed by Illumina® HumanHT beadchip microarrays. Supervised cluster analysis was used to identify genes expressed differentially at baseline between responders and non-responders based on both a difference in 28 joints disease activity score (ΔDAS28 < 1.2) and European League against Rheumatism (EULAR) response criteria after six months RTX. Genes of interest were measured by quantitative real-time PCR and tested for their predictive value using receiver operating characteristics (ROC) curves in an independent validation cohort (n = 26). Genome-wide microarray analysis revealed a marked variation in the peripheral blood cells between RA patients before the start of RTX treatment. Here, we demonstrated that only a cluster consisting of interferon (IFN) type I network genes, represented by a set of IFN type I response genes (IRGs), that is, LY6E, HERC5, IFI44L, ISG15, MxA, MxB, EPSTI1 and RSAD2, was associated with ΔDAS28 and EULAR response outcome (P = 0.0074 and P = 0.0599, respectively). Based on the eight IRGs an IFN-score was calculated that reached an area under the curve (AUC) of 0.82 to separate non-responders from responders in an independent validation cohort of 26 patients using Receiver Operator Characteristics (ROC) curves analysis according to ΔDAS28 < 1.2 criteria. Advanced classifier analysis yielded a three IRG-set that reached an AUC of 87%. Comparable findings applied to EULAR non-response criteria. This study demonstrates clinical utility for the use of baseline IRG expression levels as a predictive biomarker for non-response to RTX in RA.

Dutch rheumatologists were given a questionnaire on NSAID gastropathy, in which older age (>60 years) and previous ulcers were mentioned by them as being the most important risk factors. Dutch rheumatologists follow different strategies for the prevention of NSAID gastropathy, with a slight preference for proton pump inhibitors and the use of COX-2 selective NSAIDs.

With great interest, we read the article by Toms and colleagues [1] in the previous issue of Arthritis Research & Therapy, in which they assessed prevalences of metabolic syndrome (MetS) in rheumatoid arthritis (RA) patients. Moreover, they identified demographic and clinical factors that may be associated with MetS. Toms and colleagues found prevalences of up to 45% of MetS and demonstrated older age and health status (health assessment questionnaire) to be associated with MetS irrespectively of the definition used. Of most interest, an association between methotrexate (MTX) use and decreased presence of MetS was observed in patients more than 60 years of age. The investigators hypothesized that this may be attributed to a drug-specific effect (and not to an anti-inflammatory effect) either by changing levels of adenosine, which is known to interact with glucose and lipid metabolism, or by an indirect effect mediated through concomitant folic acid administration, thereby decreasing homocysteine levels. Recently, we also examined the prevalence of MetS in (a subgroup of) RA patients in the CARRE investigation, a prospective cohort study on prevalent and incident cardiovascular disease and its underlying cardiovascular risk factors [2]. The findings of Toms and colleagues stimulated us to perform additional analyses in our total study population (n = 353). The prevalences of MetS were 35% and 25% (Table ​(Table1)1) according to criteria of National Cholesterol Education Program (NCEP) 2004 and NCEP 2001, respectively. In multivariate backward regression analyses, we found significant associations between body mass index, pulse rate, creatinine levels, hypothyroidism and diabetes mellitus and the presence of MetS independently of the criteria used (Table ​(Table2).2). However, an independent association between single use of MTX or use of MTX in combination with other disease-modifying antirheumatic drugs, on the one hand, and a decreased prevalence of MetS, on the other hand, could not be demonstrated (even in the subgroup of patients over the age of 60). Table 1 Characteristics of the study population Table 2 Variables associated with metabolic syndrome Therefore, to get more support for a drug-specific effect, it is of interest to know whether or not in the study of Toms and colleagues the MTX effect was present only in the group of RA patients with single use of MTX or in the group of MTX-treated patients with other antirheumatic drugs. As patients with MetS were significantly older, it would give further information whether age was an independent risk factor for MetS in regression analyses. Moreover, as readers, we are not informed about comorbidities like diabetes and clinical hypothyroidism, which are notorious cardiometabolic risk factors. On the whole, we could not confirm a plausible protective role for the use of MTX and presence of MetS, and hence further investigation is required to explain the discrepancy between our findings and those of Toms and colleagues.

Introduction The aim of this study was to examine seroconversion and the relationship with age and inflammation of autoantibodies in a large group of patients attending an outpatient rheumatology clinic. Methods Levels of antibodies to citrullinated proteins/peptides (ACPAs) and IgM rheumatoid factor (IgM-RF) were determined in 22,427 samples collected from 18,658 patients. The diagnosis was derived from a diagnosis registration system. The degree of seroconversion in repeated samples and the correlation of levels with age and inflammatory markers were determined for ACPA and IgM-RF in rheumatoid arthritis (RA) and non-RA patients. Results Seventy-one percent of RA patients (n = 1,524) were ACPA-positive and 53% were IgM-RF-positive; in non-RA patients (n = 2,245), the corresponding values were 2% and 4%, respectively. In patients with at least two samples (n = 3,769), ACPA status was more stable than IgM-RF status in RA patients. ACPA- or IgM-RF-negative non-RA patients seldom became positive. ACPA positivity was unrelated to age in both RA and non-RA patients. IgM-RF positivity was unrelated to age in RA patients; however, it increased with age in non-RA patients. The correlation between autoantibody levels and inflammatory markers was low in general and was somewhat higher for IgM-RF than for ACPA. Conclusions ACPA status is more stable in time and with increasing age than IgM-RF status, further establishing its role as a disease-specific marker. ACPA and IgM-RF levels are only moderately correlated with markers of inflammation.

Infection imposes a serious burden on patients with systemic lupus erythematosus (SLE). The increased infection rate in SLE patients has been attributed in part to defects of immune defence. Recently, the lectin pathway of complement activation has also been suggested to play a role in the occurrence of infections in SLE. In previous studies, SLE patients homozygous for mannose-binding lectin (MBL) variant alleles were at an increased risk of acquiring serious infections in comparison with patients who were heterozygous or homozygous for the normal allele. This association suggests a correlation between functional MBL level and occurrence of infections in SLE patients. We therefore investigated the biological activity of MBL and its relationship with the occurrence of infections in patients with SLE. Demographic and clinical data were collected in 103 patients with SLE. Functional MBL serum levels and MBL-induced C4 deposition were measured by enzyme-linked immunosorbent assay using mannan as coat and an MBL- or C4b-specific monoclonal antibody. The complete MBL-dependent pathway activity was determined by using an assay that measures the complete MBL pathway activity in serum, starting with binding of MBL to mannan, and was detected with a specific monoclonal antibody against C5b-9. Charts were systematically reviewed to obtain information on documented infections since diagnosis of SLE. Major infections were defined as infections requiring hospital admission and intravenous administration of antibiotics. In total, 115 infections since diagnosis of lupus, including 42 major infections, were documented in the 103 SLE patients (mean age 41 ± 13 years, mean disease duration 7 ± 4 years). The percentage of SLE patients with severe MBL deficiency was similar to that in 100 healthy controls: 13% versus 14%, respectively. Although deposition of C4 to mannan and MBL pathway activity were reduced in 21% and 43% of 103 SLE patients, respectively, neither functional MBL serum levels nor MBL pathway activity was associated with infections or major infections in regression analyses. In conclusion, SLE patients frequently suffer from infections, but deficiency of functional MBL does not confer additional risk.

Rheumatoid arthritis (RA) is characterized by inflammation and an increased risk for cardiovascular disease (CVD). This study investigates possible associations between CVD and the use of conventional disease-modifying antirheumatic drugs (DMARDs) in RA. Using a case control design, 613 RA patients (5,649 patient-years) were studied, 72 with CVD and 541 without CVD. Data on RA, CVD and drug treatment were evaluated from time of RA diagnosis up to the first cardiovascular event or the end of the follow-up period. The dataset was categorized according to DMARD use: sulfasalazine (SSZ), hydroxychloroquine (HCQ) or methotrexate (MTX). Odds ratios (ORs) for CVD, corrected for age, gender, smoking and RA duration, were calculated per DMARD group. Patients who never used SSZ, HCQ or MTX were used as a reference group. MTX treatment was associated with a significant CVD risk reduction, with ORs (95% CI): 'MTX only', 0.16 (0.04 to 0.66); 'MTX and SSZ ever', 0.20 (0.08 to 0.51); and 'MTX, SSZ and HCQ ever', 0.20 (0.08 to 0.54). The risk reductions remained significant after additional correction for the presence of rheumatoid factor and erosions. After correction for hypertension, diabetes and hypercholesterolemia, 'MTX or SSZ ever' and 'MTX, SSZ and HCQ ever' showed significant CVD risk reduction. Rheumatoid factor positivity and erosions both increased CVD risk, with ORs of 2.04 (1.02 to 4.07) and 2.36 (0.92 to 6.08), respectively. MTX and, to a lesser extent, SSZ were associated with significantly lower CVD risk compared to RA patients who never used SSZ, HCQ or MTX. We hypothesize that DMARD use, in particular MTX use, results in powerful suppression of inflammation, thereby reducing the development of atherosclerosis and subsequently clinically overt CVD.

The efficacy of rifamycin SV and vancomycin againstBacteroides fragilis was compared with that of metronidazole in vitro and in vivo. The in vitro comparison was based on the MIC and on short-term growth curves, the in vivo comparison on a mixed infection withB. fragilis andEscherichia coli in a thigh infection model in mice. Rifamycin SV was about 11 times less effective than metronidazole in vivo, according to dose, and about 30 times less effective according to the mean plasma concentration. This lower efficacy could have been anticipated on the basis of the effect on in vitro grwoth curves, but not from the MIC. Vancomycin was about nine times less effective than metronidazole in vivo according to dose and about 18 times less effective according to the mean plasma concentration. The latter difference was less than would have been predicted from the results obtained in vitro, i.e., from both the effect on the growth curves and the MIC.