Development of a simple standardized scoring system for assessing large vessel vasculitis by 18F-FDG PET-CT and differentiation from atherosclerosis.

PURPOSE: This study is to develop a structured approach to distinguishing large-artery vasculitis from atherosclerosis using 18-fluorodeoxyglucose positron emission tomography combined with low-dose computed tomography (FDG PET/CT). METHODS: FDG PET/CT images of 60 patients were evaluated, 30 having biopsy-proven giant cell arteritis (GCA; the most common form of large-artery vasculitis), and 30 with severe atherosclerosis. Images were evaluated by 12 nuclear medicine physicians using 5 criteria: FDG uptake pattern (intensity, distribution, circularity), the degree of calcification, and co-localization of calcifications with FDG-uptake. Criteria that passed agreement, and reliability tests were subsequently analysed for accuracy using receiver operator curve (ROC) analyses. Criteria that showed discriminative ability were then combined in a multi-component scoring system. Both initial and final 'gestalt' conclusion were also reported by observers before and after detailed examination of the images. RESULTS: Agreement and reliability analyses disqualified 3 of the 5 criteria, leaving only FDG uptake intensity compared to liver uptake and arterial wall calcification for potential use in a scoring system. ROC analysis showed an area under the curve (AUC) of 0.90 (95%CI 0.87-0.92) for FDG uptake intensity. Degree of calcification showed poor discriminative ability on its own (AUC of 0.62; 95%CI 0.58-0.66). When combining presence of calcification with FDG uptake intensity into a 6-tiered scoring system, the AUC remained similar at 0.91 (95%CI 0.88-0.93). After exclusion of cases with arterial prostheses, the AUC increased to 0.93 (95%CI 0.91-0.95). The accuracy of the 'gestalt' conclusion was initially 89% (95%CI 86-91%) and increased to 93% (95%CI 91-95%) after detailed image examination. CONCLUSION: Standardised assessment of arterial wall FDG uptake intensity, preferably combined with assessment of arterial calcifications into a scoring method, enables accurate, but not perfect, distinction between large artery vasculitis and atherosclerosis.

Long-term effects on bone mineral density after four years of treatment with two intensive combination strategies, including initially high-dose prednisolone, in early rheumatoid arthritis patients: the COBRA-light trial.

In this study, no difference in bone loss was observed between patients with early RA initially treated with COmbinatietherapie Bij Reumatoide Artritis (COBRA) (including initially 60 mg/day prednisolone) and patients treated with COBRA-light (including initially 30 mg/day prednisolone) during 4-year observation. PURPOSE: To assess changes in bone mineral density (BMD) after 4 years in early rheumatoid arthritis (RA) patients initially treated with COBRA-light or COBRA therapy. METHODS: In a 1 year, open-label, randomised, non-inferiority trial, patients were assigned to COBRA-light (methotrexate 25 mg/week plus initially prednisolone 30 mg/day) or COBRA (methotrexate 7.5 mg/week, sulfasalazine 2 g/day plus initially prednisolone 60 mg/day) therapy. After 1 year, antirheumatic treatment was at the discretion of treating rheumatologists. BMD was measured at baseline and after 1, 2 and 4 years at hips and lumbar spine with dual-energy X-ray absorptiometry. BMD changes between treatment strategies on average over time were compared with GEE analysis. RESULTS: Data from 155 out of 162 patients could be analysed: 68% were female with a mean age of 52 (SD 13) years. Both COBRA-light and COBRA therapy showed declines in BMD at the total hip of -3.3% and -1.7%, respectively (p = 0.12), and the femoral neck, -3.7% and -3.0%, respectively (p = 0.95). At the lumbar spine, both treatment groups showed minor decline in BMD over 4 years: -0.5% and -1.0%, respectively (p = 0.10). CONCLUSION: In a treat-to-target design in early RA, over 4 years, no differences between groups were found in change in BMD at total hip, femoral neck and the lumbar spine. At the hip, bone loss was around 3% in both groups, while mild bone loss was observed at lumbar spine, both in patients starting prednisolone 60 and 30 mg/day. These data suggest that the well-known negative effects of prednisolone can be modulated by modern treatment of RA.

Coexistent subclinical hypothyroidism is associated with an increased risk of new cardiovascular events in rheumatoid arthritis: an explorative study.

Objective: Autoimmune thyroid disease often coexists with rheumatoid arthritis (RA) and is associated with elevated cardiovascular (CV) risk. However, studies in RA patients are scarce. Our aim was to investigate whether autoimmune thyroid disease increases the risk of new cardiovascular disease (CVD) in RA.Method: Thyroid-stimulating hormone (TSH) and serum free thyroxine (FT4) were assessed in 323 RA patients participating in an ongoing prospective cohort study designed to assess CV risk factors, morbidity, and mortality. Cox proportional hazard models were used to calculate hazard ratios (HRs) for new CVD and adjusted for age, gender, smoking, prevalent CVD, thyroxine replacement therapy, and RA duration.Results: Of the 323 participants, 65.3% were female, and mean ± sd age was 63 ± 7 years. At baseline, 8.1% were hypothyroid (n = 26, 16 clinical, 10 subclinical), 6.8% hyperthyroid (n = 22, 13 clinical, 9 subclinical), and 85.1% (n = 275) euthyroid. A new CV event developed in 94 patients (29.1%) during follow-up. Compared to euthyroid patients, the HR adjusted for age, gender, and prevalent CVD was 2.83 [95% confidence interval (CI) 1.13-7.09; p = 0.026] for subclinical hypothyroidism. Further adjustment for smoking, thyroxine replacement therapy, and RA duration resulted in an HR of 3.0 (95% CI 1.19-7.54; p = 0.02) for CV events in patients with subclinical hypothyroidism.Conclusion: There was no difference in CVD between RA patients with hypothyroidism and hyperthyroidism versus euthyroid patients. Coexistence of subclinical hypothyroidism with RA is associated with a higher occurrence of new CV events. Treatment trials are needed to determine whether thyroxine supplementation can further improve CV outcome in these patients.

Predictors of sick leave and improved worker productivity after 52 weeks of intensive treatment in patients with early rheumatoid arthritis.

Objective: To identify predictors of sick leave and improved worker productivity in patients with early rheumatoid arthritis (RA) treated for 52 weeks with intensive combination strategies. Methods: Patients with early RA were included in the COmbinatietherapie Bij Reumatoïde Artritis (COBRA)-light trial and followed for 52 weeks. As the COBRA-light strategy proved to be non-inferior to the COBRA strategy, all patients were pooled. Predictors for sick leave and improved worker productivity were assessed through a 3 month time-lag multivariable logistic generalized estimating equations model. Results: At baseline, 97 patients had a paid job, 59 had no job, and for six patients the work status was unknown. During the trial, 13 patients stopped working (8%) and six started working (4%). Only sick leave in the past 3 months predicted sick leave. By excluding this variable, patient global assessment and actual hours of sick leave became predictors. Increased worker productivity was predicted by higher patient global assessment levels, Sharp van der Heijde score ≥ 1, actual hours on sick leave, and higher worker productivity in the past 3 months. Conclusion: Sick leave and improved worker productivity were mainly predicted by non-disease-specific variables. Both outcomes can be predicted on a 3 month basis, using the outcome over the past 3 months for the next 3 months. By applying this model in daily practice, decisions for therapy change could be based not solely on disease activity but also taking into account a possible high risk for sick leave in the upcoming 3 months.

Suboptimal cardiovascular risk management in rheumatoid arthritis patients despite an explicit cardiovascular risk screening programme.

Objective: In 2011, we started to offer cardiovascular (CV) risk screening to rheumatoid arthritis (RA) patients with a high CV risk. After 1 year, we assessed whether patients labelled as high CV risk had started preventive treatment when indicated, and whether the CV risk score had changed. Methods: CV risk screening was performed in both a large outpatient rheumatology clinic and a general hospital in the Netherlands, and the general practitioner or the internist was informed about the results of the CV screening, including specific advice on the initiation or adjustment of cardiopreventive drugs. National guidelines were used to assess how many patients were eligible for preventive treatment. After 1 year, CV risk, lifestyle, and treatment were re-evaluated. Patients with a history of CV disease at baseline or who experienced a CV event during follow-up were excluded from the analyses. Results: A high 10 year CV risk (> 20%) was present in 58%, and 55% had an indication for anti-hypertensives, statins, or both. At follow-up, cardiopreventive drug treatment had been started or adjusted in only one-third of patients with an indication for treatment. After screening, 42% of patients reported having changed their lifestyle, through more exercise (24%), diet adaption (20%), and weight loss (11%). Conclusion: Despite clear guidelines to improve CV risk, the results of a programme comprising active screening, targeted advice, and referral to the general practitioner or internist prove that primary prevention remains a major challenge in high-risk RA patients.

One Year Effects of a Workplace Integrated Care Intervention for Workers with Rheumatoid Arthritis: Results of a Randomized Controlled Trial.

Purpose To evaluate the effectiveness of a workplace integrated care intervention on at-work productivity loss in workers with rheumatoid arthritis (RA) compared to usual care. Methods In this randomized controlled trial, 150 workers with RA were randomized into either the intervention or control group. The intervention group received an integrated care and participatory workplace intervention. Outcome measures were the Work Limitations Questionnaire, Work Instability Scale for RA, pain, fatigue and quality of life (RAND 36). Participants filled out a questionnaire at baseline, and after 6 and 12 months. We performed linear mixed models to analyse the outcomes. Results Participants were on average 50 years of age, and mostly female. After 12 months, no significant intervention effect was found on at-work productivity loss. We also found no significant intervention effects on any of the secondary outcomes. Conclusions We did not find evidence for the effectiveness of our workplace integrated care intervention after 12 months of follow up. Future studies should focus on investigating the intervention in groups of workers with severe limitations in work functioning, and an unstable work situation.

Autoantibody Specificities and Type I Interferon Pathway Activation in Idiopathic Inflammatory Myopathies.

Myositis is a heterogeneous group of autoimmune diseases, with different pathogenic mechanisms contributing to the different subsets of disease. The aim of this study was to test whether the autoantibody profile in patients with myositis is associated with a type I interferon (IFN) signature, as in patients with systemic lupus erythematous (SLE). Patients with myositis were prospectively enrolled in the study and compared to healthy controls and to patients with SLE. Autoantibody status was analysed using an immunoassay system and immunoprecipitation. Type I IFN activity in whole blood was determined using direct gene expression analysis. Serum IFN-inducing activity was tested using peripheral blood cells from healthy donors. Blocking experiments were performed by neutralizing anti-IFNAR or anti-IFN-α antibodies. Patients were categorized into IFN high and IFN low based on an IFN score. Patients with autoantibodies against RNA-binding proteins had a higher IFN score compared to patients without these antibodies, and the IFN score was related to autoantibody multispecificity. Patients with dermatomyositis (DM) and inclusion body myositis (IBM) had a higher IFN score compared to the other subgroups. Serum type I IFN bioactivity was blocked by neutralizing anti-IFNAR or anti-IFN-α antibodies. To conclude, a high IFN score was not only associated with DM, as previously reported, and IBM, but also with autoantibody monospecificity against several RNA-binding proteins and with autoantibody multispecificity. These studies identify IFN-α in sera as a trigger for activation of the type I IFN pathway in peripheral blood and support IFN-α as a possible target for therapy in these patients.

Process Evaluation of a Workplace Integrated Care Intervention for Workers with Rheumatoid Arthritis.

Purpose To perform a process evaluation of the implementation of a workplace integrated care intervention for workers with rheumatoid arthritis to maintain and improve work productivity. The intervention consisted of integrated care and a participatory workplace intervention with the aim to make adaptations at the workplace. Methods The implementation of the workplace integrated care intervention was evaluated with the framework of Linnan and Steckler. We used the concepts recruitment, reach, dose delivered, dose received, fidelity and satisfaction with the intervention. Data collection occurred through patient questionnaires and medical records. Results Participants were recruited by sending a letter including a reply card from their own rheumatologist. In total, we invited 1973 patients to participate. We received 1184 reply cards, and of these, 150 patients eventually participated in the study. Integrated care was delivered according to protocol for 46.7 %, while the participatory workplace intervention was delivered for 80.6 %. Dose received was nearly 70 %, which means that participants implemented 70 % of the workplace adaptations proposed during the participatory workplace intervention. The fidelity score for both integrated care and the participatory workplace intervention was sufficient, although communication between members of the multidisciplinary team was limited. Participants were generally satisfied with the intervention. Conclusions This process evaluation shows that our intervention was not entirely implemented as intended. The integrated care was not delivered to enough participants, but for the intervention components that were delivered, the fidelity was good. Communication between members of the multidisciplinary team was limited. However, the participatory workplace intervention was implemented successfully, and participants indicated that they were satisfied with the intervention.

Six-year follow-up study of bone mineral density in patients with systemic lupus erythematosus.

UNLABELLED: 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. INTRODUCTION: The aim of this study is to assess the BMD changes in patients with SLE and to identify the associated factors. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Depression in systemic lupus erythematosus, dependent on or independent of severity of disease.

OBJECTIVES: To estimate the prevalence of depression in subjects with systemic lupus erythematosus (SLE) in relation to the general population and to unravel the relation between depression and SLE disease characteristics. METHODS: One hundred and two subjects with SLE (mean age 44.4 years) were studied using the Beck Depression Inventory (BDI) score to estimate the prevalence of depression. The BDI scores in subjects with SLE were compared with BDI scores from a pan-European population based study (Outcome in Depression International Network (ODIN) study, n = 7934), i.e. the general population. RESULTS: The mean BDI score was higher in SLE subjects (10.1 points) compared with the BDI scores derived from the general population (10.1 versus 5.6 points, respectively, p < 0.001). This corresponds to a prevalence of depression of 16.6% and 6.7%, respectively. There was no association between disease activity or organ damage and BDI scores in subjects with SLE (p > 0.1). Only 7% of SLE subjects with high BDI scores used antidepressants. CONCLUSION: The mean BDI score and prevalence of depression are significantly higher in SLE subjects compared with the general population. No association was found between SLE disease characteristics and BDI scores. The number of depressed SLE subjects treated with antidepressants is low, suggesting inadequate recognition and treatment of depression in SLE.

Differential expression pattern of Bcl-2 family members in B and T cells in systemic lupus erythematosus and rheumatoid arthritis.

OBJECTIVE: This study aimed to evaluate the expression level of anti-apoptotic Bcl-2 family proteins in B and T cells in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in relation to disease activity and the effect of various Bcl-2 family inhibitors (BH3 mimetics) as potential treatment. METHODS: We included 14 SLE patients, 12 RA patients, and 13 healthy controls to study anti-apoptotic Bcl-2, Bcl-XL, and Mcl-1 expression and cell survival in different B and T cell subsets using stimulation assays and intracellular flow cytometry. Effect of various BH3 mimetics was assessed by cell viability analyses. RESULTS: In SLE, significant differences in Bcl-2 family members were confined to the B cell compartment with decreased induction of Bcl-XL (p ≤ 0.05) and Mcl-1 (p ≤ 0.001) upon CpG stimulation. In RA, we did not observe any differences in expression levels of Bcl-2 family proteins. Expression patterns did not correlate with disease activity apart from decreased induction of Mcl-1 in B cells in active SLE. After in vitro stimulation with CpG, plasmablasts were more viable after treatment with three different BH3 mimetics compared to naïve or memory B cells in control and patient cells. After activation, Mcl-1 inhibition was most effective in reducing plasmablast and T cell viability, however, less in patients than controls. CONCLUSION: Our study provides evidence for the increased differential expression pattern of Bcl-2 family members in B and T cell subsets of patients with SLE compared to controls. Tested BH3 mimetics showed higher efficacy in controls compared to both autoimmune diseases, though nonsignificant due to low patient numbers.

In RA patients without prevalent CVD, incident CVD is mainly associated with traditional risk factors: A 20-year follow-up in the CARRÉ cohort study.

OBJECTIVES: To extend our investigation of cardiovascular diseases (CVD) in rheumatoid arthritis (RA) patients to a follow up of more than 20 years, with a special focus on patients without prevalent CVD. METHODS: The CARRÉ study is an ongoing prospective cohort study on CV endpoints in RA patients. Results were compared to those of a reference cohort (n = 2484) enriched for type 2 diabetes mellitus (DM). Hazard ratios (HR) for RA and DM patients compared to non-RA/-DM controls were calculated with cox proportional hazard models, and adjusted for baseline SCORE1 (estimated 10-year CVD mortality risk based on CV risk factors). RESULTS: 238 RA patients, 117 DM patients and 1282 controls, without prevalent CVD at baseline were included. Analysis of events in these patients shows that after adjustment, no relevant 'RA-specific' risk remains (HR 1.16; 95%CI 0.88 - 1.53), whereas a 'DM-specific' risk is retained (1.73; 1.24 - 2.42). In contrast, adjusted analyses of all cases confirm the presence of an 'RA-specific' risk (1.50; 1.19 - 1.89). CONCLUSIONS: In RA patients without prevalent CVD the increased CVD risk is mainly attributable to increased presence of traditional risk factors. After adjustment for these factors, an increased risk attributable to RA only was thus preferentially seen in the patients with prevalent CVD at baseline. As RA treatment has improved, this data suggests that the 'RA-specific' effect of inflammation is preferentially seen in patients with prevalent CVD. We suggest that with modern (early) treatment of RA, most of the current increased CVD risk is mediated through traditional risk factors.

The autoimmune disease-associated IL2RA locus is involved in the clinical manifestations of systemic sclerosis.

Regulatory T cells (T(regs)) are crucial in the maintenance of the immune tolerance and seem to have an important role in systemic sclerosis (SSc). The interleukin 2 receptor α (IL2RA) is an important T(reg) marker, and polymorphisms of IL2RA gene are associated with a number of autoimmune diseases. Therefore, we aimed to investigate for the first time the association of the IL2RA locus in SSc. For this purpose, a total of 3023 SSc patients and 2735 matched healthy controls, from six European Caucasian cohorts, were genotyped for the IL2RA gene variants rs11594656, rs2104286 and rs12722495 using the TaqMan allelic discrimination technology. The overall meta-analysis reached statistical significance when the three polymorphisms were tested for association with SSc, the limited subtype (lcSSc) and anti-centromere auto-antibodies (ACAs). However, no significant P-values were obtained when the ACA-positive patients were removed from the SSc and lcSSc groups, suggesting that these associations rely on ACA positivity. The strongest association signal with ACA production was detected for rs2104286 (P(FDR)=2.07 × 10(-4), odds ratio=1.30 (1.14-1.47)). The associations of rs11594656 and rs12722495 were lost after conditioning to rs2104286, and allelic combination tests did not evidence a combined effect, indicating that rs2104286 best described the association between IL2RA and ACA presence in SSc.

Patients non-responding to etanercept obtain lower etanercept concentrations compared with responding patients.

OBJECTIVE: To investigate the relationship between serum etanercept levels and clinical response. METHODS: In 292 etanercept-treated patients with rheumatoid arthritis clinical and pharmacological data were determined at baseline and after 1, 4 and 6 months of etanercept treatment. Differences in etanercept levels between good, moderate and European League Against Rheumatism (EULAR) non-responders were assessed after 6 months of therapy. RESULTS: After 6 months of therapy etanercept levels were significantly higher in good responders (median (IQR) 3.78 (2.53-5.17)) compared with both moderate 3.10 (2.12-4.47) and EULAR non-responders 2.80 (1.27-3.93) (all p<0.05). There was a significant association between clinical response and serum etanercept levels (regression coefficient 0.54, 95% CI 0.21 to 0.86, p=0.001). When patients were categorised into quartiles according to the height of etanercept levels, the lowest quartile (etanercept level <2.1 mg/l) comprised 40% of all non-responders. The highest quartile (etanercept level >4.7 mg/l) comprised 35% of all good EULAR responders. Anti-etanercept antibodies were detected in none of the sera. CONCLUSION: The authors demonstrated that lower etanercept levels were associated with non-response. Therapeutic drug monitoring and the possibility of the adjusted dosing regimes in the selected groups of patients should be investigated further as a possible tool to optimise treatment with etanercept.

Subclinical renal dysfunction is independently associated with cardiovascular events in rheumatoid arthritis: the CARRÉ Study.

BACKGROUND: Patients with rheumatoid arthritis (RA) have double the risk of cardiovascular (CV) disease, largely independently of traditional CV risk factors. Renal dysfunction is associated with CV morbidity and mortality in the general population, but data on this association in RA are lacking. OBJECTIVE: To investigate the association between renal function and CV events in RA. METHODS: The CARRÉ Study is an ongoing prospective cohort study of Dutch patients with RA, which records CV events. Glomerular filtration rate (GFR) was estimated with the abbreviated Modification of Diet in Renal Disease formula. Logistic regression determined the association between estimated GFR and the occurrence of CV events. RESULTS: 353 patients were followed for 3 years, and 23 (7%) had a CV event. Patients who had an event had a significantly lower baseline GFR than those who did not (59 vs 79 ml/min, p=0.001). This association remained significant after adjustment for traditional risk factors: in this analysis, a decrease in GFR of 5 ml/min was associated with a 30% (95% CI 7% to 59%) increase in the occurrence of CV events. During follow-up, an unfavourable change in GFR was noted in patients who later had a CV event compared with those who did not. CONCLUSION: These data confirm that, in RA, renal dysfunction is associated with a higher risk of CV disease independently of traditional CV risk factors.

Receptor for advanced glycation end products (RAGE) polymorphisms are associated with systemic lupus erythematosus and disease severity in lupus nephritis.

OBJECTIVE: Interaction of advanced glycation end products (AGEs) with their receptors (RAGE) plays an important role in inflammation in auto-immune diseases. Several functional polymorphisms of RAGE have been described. In this study we analysed the role of RAGE polymorphisms in disease susceptibility for systemic lupus erythematosus (SLE). In addition, we investigated whether these polymorphisms in SLE are associated with serum levels of soluble RAGE (sRAGE), renal involvement (lupus nephritis (LN)) and its outcome. METHODS: For this cross-sectional study DNA samples of 97 SLE patients, 114 LN patients and 429 healthy controls (HC) were genotyped for four RAGE polymorphisms: -429 T/C, -374 T/A, 2184 A/G and Gly82Ser. Differences in genotype frequencies and allele frequencies were tested between patients and HCs. In SLE patients, sRAGE was measured by enzyme-linked immunosorbent assay (ELISA). In addition, association of genotypes with sRAGE and disease severity in LN was analysed. RESULTS: The C allele of -429 T/C, the T allele of -374 T/A and the G allele of 2184 A/G were significantly more prevalent in SLE and LN compared with HC. In LN, the C allele of RAGE -429 T/C, the A allele of -374 T/A and the G allele of RAGE 2184 A/G polymorphism were significantly associated with more proteinuria and worse renal function during the first two years of treatment. No association of genotype with sRAGE was found. CONCLUSION: RAGE polymorphisms are associated with susceptibility to SLE and LN. In addition, some of these polymorphisms are likely to be associated with disease severity and initial response to treatment in LN.

[Systemic autoimmune diseases; diagnostics versus classification]. / Systemische auto-immuunziekten.

Systemic autoimmune diseases are characterized by their heterogenic clinical presentations and often poorly understood pathogenesis. As such, the diagnosis process may be complex and the final diagnosis is made by an expert, after considering a differential diagnosis. Classification criteria are developed for research purposes to select homogenous populations of already diagnosed patients. In clinical practice, these classification criteria are sometimes misused as diagnostic criteria. We describe three patient histories. Two patients met the classification criteria of several separate diseases, emphasizing the amount of overlap between different sets of criteria and the necessity of making a diagnosis before using classification criteria. A third patient was diagnosed with systemic sclerosis and later developed rheumatoid arthritis; a diagnosis that could have been overlooked if classification criteria were used diagnostically. We describe the correct use of classification criteria in systemic autoimmune diseases and discuss what the diagnostic process is supposed to entail.

Beneficial effect of 1-year etanercept treatment on the lipid profile in responding patients with rheumatoid arthritis: the ETRA study.

BACKGROUND: Effective anti-inflammatory treatment with tumour necrosis factor α (TNFα) inhibitors may have favourable effects on the lipid profile. Available evidence is derived from short-term studies, and it is not clear whether TNFα inhibitors have a similar effect on the lipid profile in responders and non-responders to the treatment. OBJECTIVES: To investigate the effect of long-term etanercept treatment on the lipid profile in a large sample of patients with rheumatoid arthritis (RA), stratified for European League Against Rheumatism (EULAR) response. METHODS: Between 2004 and 2008, 292 consecutive patients with active RA (DAS28 >3.2) and a new etanercept prescription were included in an observational cohort. Clinical response variables and lipid samples were collected at baseline and after 4 months and 1 year of etanercept treatment. Generalised estimating equation analyses were used to investigate the longitudinal course of lipid levels in relation to clinical response variables. RESULTS: According to the EULAR response criteria, 76% of the patients were good or moderate responders at 4 months, and 85% of the remainder at 1 year. Significant changes in apoA-I (increased by 3.5% (p=0.002) at 4 months and 3.1% (p=0.005) at 1 year) and apoB/apoA-I ratio (decreased by 6.2% (p<0.001) at 4 months and 3.6% (p=0.025) at 1 year) were observed in EULAR responders. No significant differences were observed in EULAR non-responders at all time points. CONCLUSIONS: Treatment with etanercept resulted in a significant and sustained decrease in the apoB/apoA-I ratio in patients with good or moderate EULAR response. This may have a beneficial effect on the cardiovascular risk in patients with RA.

Circulating microparticles remain associated with complement activation despite intensive anti-inflammatory therapy in early rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterised by synovitis and joint destruction. The pathogenesis of RA is not clear, but is considered to be an immune-mediated inflammatory disorder, in which the complement system plays an important role. Although cell-derived microparticles (MPs) have been associated with inflammation and complement activation, it is unknown whether MPs are either cause or consequence. Therefore, we investigated whether circulating MPs differ between patients with very early as yet untreated arthritis and healthy controls, and whether intensive anti-inflammatory treatment of such patients affects circulating MPs. METHODS: Patients with RA (n=24) and controls (n=15) were included. Nine patients with RA were re-evaluated after 8 weeks of intensive treatment with a combination of drugs ('COmBination therapy in Rheumatoid Arthritis' (COBRA) scheme). Disease activity was measured by erythrocyte sedimentation rate (ESR), C reactive protein (CRP) and Disease Activity Score for 28 joints (DAS28). Flow cytometry was used to study MPs and exposure of complement activator molecules and complement components. RESULTS: At baseline, concentrations of MPs exposing C1q, CRP or serum amyloid-P (SAP)were all significantly elevated in patients with early RA compared to controls (p=0.003, p=0.002 and p=0.003, respectively). Upon treatment, DAS28 score, ESR and CRP levels significantly decreased (p=0.008, p=0.008 and p=0.012), but the concentrations of circulating MPs and MPs exposing complement components or activator molecules were unaffected. CONCLUSION: Circulating MPs exposing complement components or activator molecules are elevated in early RA. Since a strong anti-inflammatory therapy suppressed inflammation in patients with early RA but not levels of circulating MPs, it is unlikely that inflammation is the main underlying cause of MP release in these patients.

The metabolic syndrome is amplified in hypothyroid rheumatoid arthritis patients: a cross-sectional study.

OBJECTIVES: Rheumatoid arthritis (RA) patients are at increased risk of cardiovascular disease (CVD), which is even more pronounced in hypothyroid RA patients. An unfavourable cardiovascular risk profile conferred by a higher prevalence of the metabolic syndrome (MetS) and a higher Framingham risk score might explain this amplified cardiovascular morbidity. This study compared first, MetS (features) and second, the Framingham 10-year CVD risk in RA patients with hypothyroidism compared with euthyroid RA patients. METHODS: RA patients participating in the CARRE investigation were divided into two groups: hypothyroid and euthyroid RA patients. MetS according to the National Cholesterol Education Program Third Adult Treatment Panel criteria and the Framingham risk score was compared between hypothyroid and non-hypothyroid CVD event-free RA patients. RESULTS: In total, 257 RA patients were included: 236 with RA (91.8%) and 21 with hypothyroid RA (8.2%), respectively. The prevalence of the MetS was significantly higher in hypothyroid RA patients (43%) compared with RA patients (20%). Moreover, female hypothyroid RA patients had a higher Framingham risk score compared with euthyroid RA patients. With RA patients as the reference category, the age and gender-adjusted prevalence odds ratio for the MetS was 3.5 (95% CI 1.3 to 9.1) in hypothyroid RA. CONCLUSIONS: Hypothyroid RA patients, particularly female patients, have a more unfavourable cardiovascular risk profile, reflected by an increased prevalence of the MetS and higher Framingham score, than euthyroid RA patients, suggesting a greater need for cardiovascular risk management in these patients to prevent future CVD events.