Search

Autoreactive B cells infected by Epstein-Barr virus (EBV) are suspected to be involved in the etiology of various human chronic autoimmune diseases. This motivated us to study the relationship between peripheral blood EBV load at baseline and treatment response to B cell-depleting therapy in rheumatoid arthritis (RA) patients. Thirty-five RA patients who started treatment with rituximab (RTX) in a routine clinical setting were assessed for baseline disease activity using disease activity score using 28 joint counts (DAS28) (erythrocyte sedimentation rate [ESR]). Treatment response was evaluated 3–7 months after RTX. EBV load in baseline whole blood (WB) samples was determined using quantitative PCR. EBV DNA was detected in 16/35 (46 %) of the WB samples. In these 16 EBV-positive patients, the median viral load was 3.15 (2.68–4.00) log copies/ml. Good/moderate European League Against Rheumatism (EULAR) response was observed in 16/16 of the EBV DNA-positive vs 13/19 EBV DNA-negative patients, p = 0.022. Significant response (DAS28 change >1.2) was observed in 14/16 of the EBV DNA-positive vs 10/19 EBV DNA-negative patients, p = 0.035. The decline in DAS28 after RTX was 2.10 (1.03–4. 78) in the EBV DNA-positive vs 1.47 (−0.7–4.70) in the EBV DNA-negative patients, p = 0.13. EBV load at baseline significantly correlated with change in DAS28 after RTX (τB = −0.261, p = 0.042). Our results suggest that the presence of EBV genome in WB could serve as a predictive marker to RTX therapy in RA.

Objective Many cytokines involved in RA activate the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways. Therapeutic drugs that inhibit these pathways are being developed for RA. To investigate disease-related alterations in the activity of JAK-STAT pathways in RA, we studied the expression and activation of STAT1 and STAT3 in unstimulated and cytokine-stimulated cells and determined the levels of circulating cytokines. Methods The expression of STAT1 and STAT3 mRNA in peripheral blood (PB) and SF T cells and monocytes was studied in RA patients and healthy volunteers by RT-PCR. Basal and cytokine (IFN-γ, IL-6, IL-10)-induced STAT phosphorylation was analysed in PB T cells and monocytes using multicolour flow cytometric analysis. Results STAT3 mRNA levels were up-regulated in both PB and SF T cells and monocytes from RA patients. STAT1 expression was elevated in SF monocytes. The levels of phospho-STAT3 in resting PB T cells and monocytes were significantly higher in patients with RA than in healthy volunteers. IL-6 levels were elevated in RA plasma and correlated with the level of STAT3 phosphorylation in CD4(+) T cells and monocytes. IL-6-mediated STAT3 activation was deregulated in T cells from RA patients. IL-6-induced phosphorylation of STAT3 was decreased in CD4(+) T cells from patients with high plasma IL-6 levels and constitutive STAT3 phosphorylation. Conclusion The results suggest that IL-6 induces hyperactivation of STAT3 in circulating immune cells in active RA, and this subsequently desensitizes the IL-6 response in T cells.

Objective. A European League Against Rheumatism (EULAR) SS disease activity index (ESSDAI) and a patient-reported index (ESSPRI) have recently been developed and validated. In our previous study the ESSDAI correlated significantly with serum b2 microglobulin concentration. We now aim to establish whether the ESSPRI is also associated with serum b2 microglobulin or with other patient-reported indices. Methods. The data on 100 consecutive visits of patients with primary SS (pSS) were reviewed from the patient charts. Patients who had filled out the ESSPRI questionnaire and fulfilled at least four of the revised AmericanEuropean consensus group criteria for pSS were included. Data were gathered on the ESSPRI (010 cm) and on the patient’s global health assessment [visual analogue scale (VAS) 010 cm] (PGH-VAS), pain-VAS (010 cm) and HAQ (range 03). Results. The ESSPRI correlated significantly with the PGH-VAS (r = 0.753, P < 0.0001), pain-VAS (r = 0.656, P < 0.0001) and HAQ (r = 0.542, P < 0.0001) (Spearman’s correlation). It also correlated weakly with serum b2 microglobulin (r = 0.214, P = 0.043) and ESR levels (r = 0.235, P = 0.019). Conclusion. The ESSPRI correlated significantly with other patient-reported indices, serum b2 microglobulin and ESR in patients with pSS. Our results support the view that the ESSPRI is a useful tool in the follow-up of patients with pSS.

Objective To study whether adding initial infliximab to remission-targeted initial combination-DMARD treatment improves the long-term outcomes in patients with early rheumatoid arthritis (RA). Methods Ninety-nine patients with early, DMARD-naive RA were treated with a triple combination of DMARDs, starting with methotrexate (max 25 mg/week), sulfasalazine (max 2 g/day), hydroxychloroquine (35 mg/kg/week), and with prednisolone (7.5 mg/day), and randomised to double blindly receive either infliximab (3 mg/kg; FIN-RACo+INFL) or placebo (FIN-RACo+PLA) infusions during the first 6 months. After 2 years the treatment strategies became unrestricted, but the treatment goal was strict ACR remission. At 5 years the clinical and radiographic outcomes were assessed. Results Ninety-one patients (92%) were followed up to 5 years, 45 in the FIN-RACo+INFL and 46 in the FIN-RACo+PLA groups. At 5 years, the respective proportions of patients in strict ACR and in disease activity score 28 remissions in the FIN-RACo+INFL and FIN-RACo+PLA groups were 60% (95% CI 44% to 74%) and 61% (95% CI 45% to 75%) (p=0.87), and 84% (95% CI 71% to 94%) and 89% (95% CI 76% to 96%) (p=0.51). The corresponding mean (SD) total Sharp/van der Heijde scores at 5 years were 4.3 (7.6), and 5.3 (7.3), while the respective mean Sharp/van der Heijde scores changes from baseline to 5 years were 1.6 (95% CI 0.0 to 3.4) and 3.7 (95% CI 2.2 to 5.8) (p=0.13). Conclusions In early RA, targeted treatment with a combination of traditional DMARDs and prednisolone induces remission and minimises radiographic progression in most patients up to 5 years; adding initial infliximab for 6 months does not improve these outcomes.

Objectives To investigate the use of DMARDs and biologic treatments and disease activity in patients with JIA referred to the adult rheumatology clinic and to provide further information regarding the need for long-term rheumatologic care. Methods We studied the data of 154 patients retrospectively from hospital records if they met the following criteria: diagnosis of JIA and at least one visit to the adult rheumatologic unit. Previous and current antirheumatic treatment, duration of biologic therapy and disease activity were recorded. Results At the end of patient follow-up, the median age of the eligible patients was 19 years (range 16-24 years) and the disease duration was 8 years (range 0-20 years). Twenty-nine per cent of the patients were still on biologic therapies. The total median duration of treatment with at least one biologic agent was 4.2 years, and 44% of treatment durations lasted >5 years. Some disease activity was present in the last year in 58% of patients. Activity in the temporomandibular joint was detected in 14% and uveitis in 8%. Thirteen per cent did not need further specialist care and in 14% all antirheumatic medication could be tapered off. Conclusion Almost one-third of adolescents and young adults with JIA who needed specialist care were on biologics. The need for treatment in many cases is long term (>5 years). Most patients (58%) still showed evidence of mild disease activity. Adolescents and young adults with JIA are a distinct patient group in adult health care and a specialized multidisciplinary approach to treatment is needed.

Predicted versus observed radiographic progression in early rheumatoid arthritis (POPeRA) was applied to demonstrate how various treatment modalities affect and potentially minimise radiographic progression over time.The POPeRA method utilises the baseline radiographic score and patient-reported symptom duration to predict radiographic outcomes. It was applied at baseline, 2, and 5 years to patients with eRA from the randomised Finnish RA Combination trial (FIN-RACo) (n=144) and New Finnish RA Combination Therapy (NEO-RACo) (n=90) trials. For FIN-RACo, patients were randomised either to a single DMARD (sulfasalazine, with or without prednisolone) or to combination therapy (methotrexate+sulfasalazine+hydroxychloroquine, i.e. triple therapy, with prednisolone). In NEO-RACo, all patients were assigned intensified combination therapy (including 7.5 mg prednisolone/day) plus a randomised 6-month induction of either placebo or anti-TNF treatment (infliximab).In FIN-RACo, combination versus monotherapy resulted in superior outcomes in the change from predicted progression over 2 and 5 years (mean 35.7% reduction vs. -32.9%, a worsening from predicted, p=0.001; 34.2% vs. -17.8%, p=0.003, respectively). In NEO-RACo, combination+anti-TNF induction led to significantly greater reductions from predicted progression than combination+placebo, both at 2 and 5 years of follow-up (98.5% vs. 83.4%, p=0.005; 92.4% vs. 82.5%, p=0.027, respectively). Importantly, anti-TNF add-on led to superior reductions from predicted among RF-positive patients (2 years: 97.4% vs. 80.4%, p=0.009; 5 years: 90.2% vs. 80.1%, p=0.030), but not among RF-negative patients.These results confirm that conventional combination therapy in eRA has a long-term radiographic benefit versus monotherapy. Through POPeRA, it was made evident that anti-TNF induction therapy for 6 months further increases the long-term radiographic benefit of combination therapy in RF-positive patients.

ObjectiveEarly treatment of patients with rheumatoid arthritis (RA) with combination treatment starting with methotrexate, sulfasalazine, hydroxychloroquine and prednisolone (FIN-RACo strategy) is superior to monotherapy. A study was undertaken to determine whether infliximab (INFL) added to intensified FIN-RACo treatment for the initial 6 months improves the 2-year outcome.Methods99 patients with early untreated active RA were enrolled in an investigator-initiated, randomised, double-blind, multicentre, parallel-group trial. Primary outcomes were remission and radiological changes at 2 years. All patients started with FIN-RACo. In addition, they were randomised to receive INFL or placebo (Pla) from weeks 4 to 26.ResultsAt 24 months, 66% and 53%, respectively, of the patients in the FIN-RACo+INFL and FIN-RACo+Pla groups were in remission according to the modified American College of Rheumatology (ACR) criteria (p=0.19), 26% and 10% were in sustained modified ACR remission (p=0.042) and 82% in both groups were in remission by 28-joint disease activity score (not significant). Mean changes in the total Sharp-van der Heijde score were 0.2 and 1.4, respectively (p=0.0058).ConclusionsMost patients with early active RA achieve clinical remission and develop negligible joint damage with the intensified FIN-RACo regimen. Adding INFL for the first 6 months delays radiological progression.

To determine which disease-modifying anti-rheumatic drugs (DMARDs) are currently used by Finnish rheumatologists to treat early rheumatoid arthritis (RA).Information on sex, date of birth, and date of special medicine reimbursement decision for all new RA patients was collected from a nationwide register maintained by the Social Insurance Institution (SII) during the time period from 1 January 2000 to 31 December 2007. Patient cohorts were registered in 2-year time periods (2000-01, 2002-03, 2004-05, 2006-07) and DMARDs purchased by the patient cohorts during the first year after the date of reimbursement decision for RA were registered. The frequencies of early drug treatment strategies (combination of DMARDs, single DMARD, or no DMARDs) were evaluated.A total of 14 878 (68.0% female, 62.6% rheumatoid factor (RF)-positive) patients were identified. Between 2000 and 2001 the most commonly used treatment strategy for early RA during the first 3 months was single DMARD treatment (56.1%) and the most commonly used DMARD during the first year was sulfasalazine (63.0%), while between 2006 and 2007 the respective treatments were combination DMARDs (55.3%) and methotrexate (69.0%). The change in treatment strategies as well as in DMARDs used was highly significant (p0.001 for linearity). At the end of the study period only 4.9% of the patients with early RA were not receiving DMARDs during the first 3 months.Currently, combination therapy including methotrexate is the most commonly prescribed treatment strategy for early RA in Finland. In recent years, an increasing number of active drug treatments have been taken into practice.

We studied 71 patients with acute Yersinia infection for the occurrence of pathologic urinary and renal findings. Transient proteinuria and/or microhematuria was found in 17 patients (24%) and slightly elevated serum creatinine in seven patients (10%). Renal biopsy was done in two patients and revealed mild mesangial glomerulonephritis in both cases. One of these patients had IgA glomerulonephritis and Reiter's syndrome. Pyuria occurred in 16 patients (23%) and was frequently associated with Reiter's syndrome. Seventy-three patients with acute intrinsic renal failure were studied for the occurrence of acute Yersinia infection by determining Yersinia antibodies by ELISA. One out of 13 patients with acute glomerulonephritis but none of 60 patients with acute tubulointerstitial renal disease had acute Yersinia infection. Acute Yersinia infection seems to be rarely an etiologic factor in acute intrinsic renal failure. Our results indicate that transient proteinuria, microhematuria, pyuria or impaired renal function are frequent findings in patients with acute Yersinia infections. However, glomerulonephritis seems to be a rather infrequent and mild complication of acute Yersinia infection.

Objective.To evaluate the 5-year incidence of cervical spine disorders in patients with early rheumatoid arthritis (RA) treated by 2 different disease modifying antirheumatic drug (DMARD) strategies.Methods.In a national, multicenter, prospective FIN-RACo-trial, a cohort of 199 patients with early, clinically active RA was randomly assigned to treatment with a combination of 3 DMARD and prednisolone (Combi group) or with a single DMARD (Single group) with or without prednisolone, aiming to induce remission. After 2 years, the DMARD therapy was unrestricted. Lateral view cervical spine radiographs during full flexion and extension were taken at the 5-year followup visits. The presence of anterior atlantoaxial subluxation (aAAS), atlantoaxial impaction (AAI), and subaxial subluxation (SAS) was assessed in the 149 patients with radiographs available (80 Single and 69 Combi).Results.At the 5-year visits, aAAS, AAI, and SAS were found in 13 (9%), 6 (4%), and 9 (6%) patients, respectively. The corresponding Single/Combi group ratios were 11/2, 5/1, and 5/4. Of the baseline data, only poor physical function [Health Assessment Questionnaire (HAQ); p = 0.024] and Single treatment strategy (p = 0.019) were significantly associated with aAAS. Worse HAQ scores and Disease Activity Score 28 values were found in patients who developed aAAS during the 5-year followup.Conclusion.RA patients with sustained clinical disease activity and poor HAQ are at increased risk of developing aAAS. The development of aAAS during the first 5 years of RA was rare among the patients treated with a combination of DMARD for at least 2 years from the diagnosis. Intensive treatment with traditional DMARD prevents or retards the development of aAAS in patients with recentonset RA.

To describe the effects of rituximab therapy in patients with rheumatoid arthritis (RA) in routine clinical practice in Finland.Data were collected retrospectively from patient records in five rheumatology clinics in Finland. All RA patients treated during 2005-2008 (n = 81) were included. Information on disease-modifying anti-rheumatic drugs (DMARDs), DMARD combinations, and biologics prior to rituximab use was collected as well as treatment responses after initiating rituximab therapy. The Disease Activity Score using 28 joint counts (DAS28) was used to determine disease activity and European League Against Rheumatism (EULAR) responses.Mean disease duration was 14 (range 0-47) years and the median number of prior DMARDs and biologics used were 7 (1-12) and 2 (0-4), respectively. Efficacy analysis was performed on 57 patients with available DAS28 data at treatment onset and follow-up visits. Median DAS28 declined from 6.07 (3.19-7.70) to 3.99 (1.53-6.55) by the first rituximab treatment course. Altogether 77% of the patients achieved a EULAR response, 26% with a good response including 18% with remission. Furthermore, the patients treated concomitantly with DMARDs other than methotrexate (MTX) achieved a EULAR response slightly more often than the patients on MTX (85% vs. 70%) only. A second course of rituximab was given to 48% of the patients on an average of 9 months after initial therapy, with the median DAS28 score declining further to 3.49 (0.1-5.74). Safety and tolerability assessment of the 81 patients indicates rituximab to be well tolerated.Rituximab can effectively control disease activity in patients with active disease and poor response to previous therapies, in combination with MTX but also with other DMARDs.

Background/Aim: Knowledge of the usefulness of cystatin C measurement in the detection of chronic kidney disease in patients with rheumatoid arthritis (RA) is scant. The purpose of this study was to evaluate the ability of plasma cystatin C- and creatinine-based methods to predict glomerular filtration rate (GFR) and classify chronic kidney disease in RA patients. Methods: The study population consisted of 64 RA patients aged 41–86 years. Comparisons were made between measured plasma creatinine, cystatin C, creatinine clearance and GFR estimated by the Cockcroft-Gault (CG) and the Modification of Diet in Renal Disease (MDRD) formulas. The plasma clearance of 51Cr-EDTA served as a reference. Results: The Pearson correlation coefficients between plasma clearance of 51Cr-EDTA and the markers of GFR were calculated. The correlation coefficients were 0.800 for plasma creatinine, 0.863 for cystatin C, 0.866 and 0.904 for GFR values estimated by MDRD and CG and 0.922 for plasma creatinine clearance. Statistically significant differences were detected between the correlation coefficients of plasma creatinine and GFR estimated by CG (p = 0.0412) and plasma creatinine and creatinine clearance (p = 0.0099). Creatinine clearance and the MDRD and CG formulas proved to be better at identifying GFR Conclusion: We recommend using the CG formula or creatinine clearance for the estimation of the GFR of RA patients instead of solely creatinine or cystatin C in clinical work.

To determine from single-centre data the treatment continuation, discontinuation, and reasons for discontinuation among the patients with active rheumatoid arthritis (RA) or spondyloarthropathies (SpA) who were treated with infliximab as their first biological anti-rheumatic drug.All (n = 104) RA and SpA patients who were treated with infliximab as their first biological treatment according to the national guidelines in the Centre for Rheumatic Diseases, Tampere University Hospital during 1999-2005 were analysed at baseline and after 6 months of treatment. The treatment was regarded as ineffective if the response was lower than American College of Rheumatology (ACR) response criteria ACR50 in RA or the reduction of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was lower than 50% or 2 cm in SpA.After 6 months, 71% of the patients continued infliximab treatment and the prednisolone dose was diminished by 40%. Infliximab was discontinued in 30 patients and seven of them discontinued due to remission. Eight patients were regarded as poor responders. Thirteen patients discontinued because of adverse events, mainly infections and hypersensitivity reactions. One patient discontinued the treatment because of drug-related leucopaenia and one because of elevated aminotransferases.In this study, infliximab treatment was started in patients who had active disease despite ongoing treatment with combinations of disease-modifying anti-rheumatic drugs (DMARDs). Seventy-eight per cent achieved at least 50% response when infliximab was added to their DMARD treatment. Adverse events, mainly infections and hypersensitivity reactions, were in line with previous reports. Two rare adverse events were reported, one patient with leucopaenia and one with elevated aminotransferases.

In the present study, we determined from a single-center data the treatment continuation, discontinuation and reasons for discontinuation in the patients with active rheumatoid arthritis (RA) or spondyloarthropathies (SpA) who were treated with etanercept or adalimumab. All RA and SpA patients, who were treated with etanercept (n = 53) or adalimumab (n = 43) as their first biological treatment according to national guidelines in the Center for Rheumatic Diseases, Tampere University Hospital during the years 1999-2005, were analyzed at baseline and after 1-year treatment. The treatment was regarded ineffective if the clinical response was lower than ACR50 in RA or the reduction of BASDAI was lower than 50% or 2 cm in SpA. After 1 year, the continuation rate was 74% with etanercept and 60% with adalimumab. Mean prednisolone dose among continuers was diminished by 52% in etanercept-treated patients and by 44% in adalimumab-treated patients. During 1-year follow-up, 14 (26%) of the etanercept-treated patients and 17 (40%) of the adalimumab-treated patients discontinued the medication. Eleven patients were regarded as poor responders, seven in etanercept group and four in adalimumab group. Adverse events (mainly infections and injection reactions) caused six discontinuations in etanercept-treated group and 11 discontinuations in adalimumab-treated group. Etanercept was discontinued due to other adverse event in two patients: in one patient due to adenocarcinoma of ovary and in one patient due to drug-related leukopenia. One patient treated with adalimumab developed clinical and immunological features of systemic lupus erythematosus (SLE). In the present study, etanercept and adalimumab treatments were started in patients who had active RA or SpA despite ongoing treatment with combinations of traditional disease modifying antirheumatic drugs (DMARDs). Thirty-nine (74%) patients and twenty-six (60%) patients achieved at least 50% response when etanercept or adalimumab was added to their earlier DMARD treatment. Adverse events (mainly infections and injection reactions) were in line with previous reports. Three rare adverse events were reported: one patient with ovarial carcinoma, one with leukopenia and one with features of drug-induced SLE.

1,5Objectives. Cytokines play a key pathogenic role in rheumatoid arthritis (RA). Several cytokines signal through the JAK-STAT pathway,which is negatively regulated by the suppressors of cytokine signalling (SOCS) proteins. Since SOCS protein levels can profoundly modulatecellular responses to cytokines, we have investigated their expression in chronic RA.Methods. The levels of SOCS1–3 and CIS1 mRNA in peripheral blood (PB) and synovial fluid (SF) mononuclear cells (MCs), purified T cellsand monocytes from RA patients and healthy volunteers were studied using quantitative reverse transcriptase polymerase chain reaction(RT-PCR). SOCS mRNA and protein expression in synovial tissues were examined by RT-PCR and immunohistochemistry.Results. The levels of SOCS1 and SOCS3 were significantly increased in PBMCs from RA patients when compared with healthy volunteers.These differences were mainly due to up-regulation of SOCS1 in PB T cells and of SOCS3 in PB monocytes. In addition, SOCS2 wasup-regulated in PB T cells. Interestingly, SF T cells expressed lower and SF macrophages higher levels of SOCS molecules than their PBcounterparts. Similarly, while a significant portion of macrophages in synovial tissues expressed SOCS1 and SOCS3 proteins, the majority ofT cells remained SOCS negative. Finally, SOCS1 was up-regulated in the synovial membranes from patients with RA when compared withosteoarthritis.Conclusions. SOCS expression levels are profoundly altered in RA, and the profile of SOCS expression is dependent on both the cell typeas well as the cellular compartment.K

The objective of this study was to assess the long-term prognosis of nephropathy findings and the incidence of new abnormal clinical renal findings in patients with rheumatoid arthritis (RA). The original population-based cross-sectional study of 604 RA patients was carried out in 1988, 103 nephropathy patients being found. Controls matched for age, sex, and duration of RA were selected from among RA patients with normal renal function and urinalysis in 1988. In 2003, a follow-up study was made of the 103 nephropathy patients and 102 controls, and the median follow-up time was 13 years. In the original nephropathy group, serum creatinine exceeded 200 mumol/l in 8% of the original isolated hematuria patients, in 30% of the isolated proteinuria patients, in 57% of the combined hematuria and proteinuria patients, but in none of the isolated chronic renal failure (CRF) patients (p = 0.001 for the difference). Probable or definitive renal amyloidosis was diagnosed in 19% of the nephropathy patients. Dialysis therapy was given to 10 out of the 103 nephropathy patients, nine of them belonging to the original isolated proteinuria or combined hematuria and proteinuria groups. There were six renal deaths among the nephropathy patients, and none in the controls. In the control group, new abnormal renal findings, in most cases mild, were detected in 28%. Serum creatinine exceeded 200 mumol/l in 4% of the controls, and dialysis therapy was given to 2% of the controls. Probable or definitive renal amyloidosis was diagnosed in 4% of this group. With regards to the development or progression of chronic renal failure, the long-term clinical prognosis of isolated hematuria and isolated CRF was found to be favorable. Proteinuria alone or combined with hematuria or CRF was related to evidently poorer prognosis.

To explore the cost of the statutory inpatient rehabilitation system in Finland and its impact on the functional and work capacity of patients with early rheumatoid arthritis (RA).In the Finnish Rheumatoid Arthritis Combination-Therapy trial (FIN-RACo), 195 patients with recent-onset RA, 162 of them available for the work force, were randomly assigned to two different drug treatment strategies for 2 years. Otherwise, the patients received routine multidisciplinary care and, if their functional or work capacity was endangered, were referred to inpatient rehabilitation. After a 5-year follow-up, data on rehabilitation, sick leave, and RA-related disability pensions were obtained from official registers.Of the 162 patients, 49 (30%) underwent inpatient rehabilitation at an average cost of EURO5400. The rehabilitated patients more often worked in white-collar jobs and had more pain and a worse Health Assessment Questionnaire (HAQ) score (1.0 vs. 0.78; p = 0.01) at baseline. Their HAQ scores remained higher throughout follow-up (p0.001); no change appeared over inpatient periods [mean 0.01; 95% confidence interval (CI) -0.13 to 0.16]. No independent impact of rehabilitation on the HAQ score emerged in an adjusted generalized estimating equations (GEE) model (p = 0.55). Nor did any improvement in work capacity appear: average lost productivity (human capital approach) per patient-year was EURO10 155 (95% CI 6994-14 196) before and EUR 12 839 (95% CI 8589-19 139) after the start of rehabilitation.For patients with recent-onset RA, the Finnish statutory inpatient rehabilitation system had no positive impact on either functional or work capacity during the first few years, despite its considerable cost.

Objective The aim of this study was to explore the cost-effectiveness of biological DMARDs (bDMARDs) compared with conventional synthetic DMARDs (csDMARDs) for RA using real-world data from Finnish registers. Methods RA patients starting their first bDMARD and comparator patients using csDMARDs during 2007-11 were obtained from the National register of biologic treatments in Finland and the Jyvaskyla Central Hospital patient records. Propensity score matching was applied to adjust for differences between bDMARD and csDMARD users. Effectiveness was measured in quality-adjusted life years (QALY) and based on the register of biologic treatments in Finland and Jyvaskyla Central Hospital patient records, whereas the direct costs were obtained from relevant Finnish national registers. Patients were followed up for 2 years, and both costs and effectiveness for the second year were discounted at 3%. The incremental cost-effectiveness ratio (ICER) with 95% CI was calculated based on bootstrapped mean costs and effectiveness. Results Of 1581 RA patients meeting study inclusion criteria, 552 bDMARD and 220 csDMARD users were included in analyses after matching. Mean costs for bDMARDs and csDMARDs were €55 371 and €24 879, while mean effectiveness was 1.23 and 1.20 QALYs, respectively. Consequent ICER was €902 210/QALY. Results were confirmed in sensitivity analyses. Conclusion The high incremental cost and the small, non-significant difference in effectiveness resulted in high ICER, suggesting that bDMARDs are not cost-effective. Regardless of matching, latent confounders may introduce bias to the results.

To evaluate the volumetric brain magnetic resonance imaging (MRI) findings in a population-based sample of systemic lupus erythematosus (SLE) patients and to detect a possible relationship between cerebral MRI abnormalities and specific neuropsychiatric (NP) manifestations.The study population consisted of patients with SLE (n = 43) in Pirkanmaa Health Care District, Finland and of a sex- and age-stratified reference group from the general population (n = 43). In addition to a clinical neurological investigation, all subjects received a detailed neuropsychological assessment and an MRI study. Volumetric measures of cerebral atrophy as well as T1- and T2-weighted lesions were obtained. SLE activity was assessed by the European Consensus Lupus Activity Measure (ECLAM) index, and accumulated NP abnormalities were measured by the Systemic Lupus International Collaborating Clinics (SLICC) damage index. A cumulative lifetime dose of glucocorticoids was determined from the patientrecords.Compared with controls, SLE patients had increased volumes of both T1- and T2-weighted lesions (p = 0.019 and p0.0001, respectively) and increased cerebral atrophy (p0.001). All the measured MRI parameters were statistically significantly higher in NPSLE than in non-NPSLE patients. In SLE patients, cerebral atrophy was associated with cognitive dysfunction, epileptic seizures, and cerebrovascular disease; T1-weighted lesions were associated with epileptic seizures and T2-weighted lesions with cognitive dysfunction. All MRI parameters correlated significantly with the SLICC index but not with the ECLAM index. A positive correlation was found between a cumulative dose of glucocorticoids and cerebral atrophy in SLE patients.MRI abnormalities, including brain atrophy and T1- and T2-weighted lesions, are significantly more common in patients with SLE than in the general population and they are related to specific NP manifestations. Our findings also provide support for the organic aetiology of cognitive dysfunction in SLE.

Objective To explore the impact of an early treatment response on maintenance of work capacity in patients with early, active rheumatoid arthritis (RA). Methods In the Finnish Rheumatoid Arthritis Combination Therapy trial, 195 patients with recent-onset RA were randomized to receive either a combination of disease-modifying antirheumatic drugs (DMARDs) with prednisolone or a single DMARD with or without prednisolone for 2 years. Treatment responses were evaluated according to the American College of Rheumatology (ACR) criteria. After a 5-year followup, the cumulative number of days of sick leave and RA-related permanent work disability was calculated for each of the 162 patients who were available for the active work force at baseline. Results Of the 159 patients assessed at 6 months, 29 were in clinical remission, 66 achieved an ACR50 response but not remission, 29 achieved an ACR20 response but not an ACR50 response, and 35 failed to achieve an ACR20 response. In these 4 groups, the median numbers of work disability days per patient-year from 6 months through 60 months of followup were 0 (interquartile range [IQR] 0–3), 4 (IQR 0–131), 16 (IQR 0–170), and 352 (16–365), respectively (P < 0.001). Pairwise multiple comparisons showed a statistically significant difference between all groups except the ACR50 and ACR20 groups. At 12 months, 30 patients were in remission. None of the 44 patients in remission at 6 or 12 months became permanently work disabled over the 5-year followup, as compared with 15 patients in the ACR50 group (23%), 6 in the ACR20 group (21%), and 19 without an ACR20 response at 6 months (56%). Conclusion Prompt induction of remission translates into maintenance of work capacity. At 6 months, an ACR50 response is no better than an ACR20 response with regard to future productivity, while failure to achieve an ACR20 response carries a high risk for work disability.

Objective To evaluate the long-term frequency of disease remissions and the progression of joint damage in patients with early rheumatoid arthritis (RA) who were initially randomized to 2 years of treatment with either a combination of 3 disease-modifying antirheumatic drugs (DMARDs) or a single DMARD. Methods In this multicenter prospective followup study, a cohort of 195 patients with early, clinically active RA was randomly assigned to treatment with a combination of methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone or with a single DMARD (initially, sulfasalazine) with or without prednisolone. After 2 years, the DMARD and prednisolone treatments became unrestricted, but were still targeted toward remission. The long-term effectiveness was assessed by recording the frequency of remissions and the extent of joint damage seen on radiographs of the hands and feet obtained annually up to 5 years. Radiographs were assessed by the Larsen score. Results A total of 160 patients (78 in the combination group and 82 in the single group) completed the 5-year extension study. At 2 years, 40% of the patients in the combination-DMARD group and 18% in the single-DMARD group had achieved remission (P < 0.009). At 5 years, the corresponding percentages were 28% and 22% (P not significant). The median Larsen radiologic damage scores at baseline, 2 years, and 5 years in the combination-DMARD and single-DMARD groups were 0 and 2 (P = 0.50), 4 and 12 (P = 0.005), and 11 and 24 (P = 0.001), respectively. Conclusion Aggressive initial treatment of early RA with the combination of 3 DMARDs for the first 2 years limits the peripheral joint damage for at least 5 years. Our results confirm the earlier concept that triple therapy with combinations of DMARDs contributes to an improved long-term radiologic outcome in patients with early and clinically active RA.

To assess the mortality and causes of death in a cross-sectional population-based study of 1042 patients with rheumatoid arthritis (RA).In 1988, 604 RA patients [470 females (F), 134 males (M)] and 457 age- and sex-matched controls (352 F, 105 M) were examined prospectively (participants) and 438 (183 F, 81 M) non-participant RA patients retrospectively. In 1999, vital status and causes of death were determined. Mortality in the total RA population was compared to that in the general population, and that among participant RA patients to their matched controls.A total of 384 (37%) RA patients and 71 (16%) controls died. RA patients had increased mortality compared to the general population (standardized mortality ratios SMR 2.64) or controls (1.71). This was observed in both sexes. Over 40% of deaths in all groups were due to cardiovascular diseases. RA patients were at increased risk of dying of urogenital, gastrointestinal, respiratory and cardiovascular diseases, infections, and cancers when compared to the general population or controls.Our results show that a cross-sectional cohort of RA patients had an increased risk of death from various causes.

Objective To compare the efficacy of therapy with a combination of disease-modifying antirheumatic drugs (DMARDs) versus therapy with a single DMARD in the prevention of work disability in patients with early rheumatoid arthritis (RA). Methods In the Finnish Rheumatoid Arthritis Combination Therapy trial, 195 patients with recent-onset RA were randomly assigned to receive either combination therapy with DMARDs (sulfasalazine, methotrexate, hydroxychloroquine) plus prednisolone or single therapy with a DMARD with or without prednisolone. After 2 years, the drug treatment strategy was no longer restricted. At baseline, 162 patients (80 in the combination-treatment group and 82 in the single-treatment group) were still working or at least available for work. After 5 years of followup, data on all sick leave and retirement were obtained from social insurance registers or case records. The main outcome for each patient was the cumulative duration of all sick leaves and RA-related disability pensions, divided by the observation period during which the patient was not retired because of another disease or because of age. Results The cumulative duration of work disability per patient-observation year was significantly lower in those randomized to combination therapy than in those randomized to single therapy: median 12.4 days (interquartile range [IQR] 0–54) versus 32.2 days (IQR 6–293) (P = 0.008, sex- and age-adjusted P = 0.009). This was mainly due to the difference in sick leaves (i.e., work disability periods ≤300 days): median 11.7 days (IQR 0–44) per patient-observation year in those treated with combination therapy and 30.0 days (IQR 6–68) in those treated with single therapy (P = 0.002). No statistically significant difference was seen in RA-related disability pensions. Conclusion Aggressive initial treatment of RA with a combination of DMARDs improves 5-year outcome in terms of lost productivity in patients with RA of recent onset.

Background: The value of antibiotics in the treatment of reactive arthritis (ReA) is still controversial. Objectives: To analyse the long term outcome of patients with ReA, treated with a three month course of ciprofloxacin or placebo. Methods: Patients who had had ReA and had participated in a double blind, placebo controlled trial on the effectiveness of ciprofloxacin 4–7 years earlier were invited to a clinical examination. Of the 71 patients who were included in the original study, 53 agreed to visit the clinic for an examination. Twenty six of 53 patients had originally received ciprofloxacin and 27 had belonged to the placebo group. Of these, 20 in the ciprofloxacin and 25 in the placebo group were HLA-B27 positive. Results: 11/27 (41%) patients in the original placebo group had now developed chronic rheumatic disease, as compared with only 2/26 (8%) patients originally treated with ciprofloxacin (p=0.006). Two patients who originally had received placebo, none in the ciprofloxacin group had developed ankylosing spondylitis, and three patients in the original placebo group, none in the ciprofloxacin group had recurrent anterior uveitis. The same tendency was seen when several different measures were analysed. Of the patients with chronic spondyloarthropathy, 10 in the placebo and none in the ciprofloxacin group were HLA-B27 positive. Conclusion: Analysis 4–7 years after the initial ReA suggests that a three month course of antibiotics in the acute phase may have a beneficial effect on the long term prognosis.

To study the effects of Lactobacillus rhamnosus GG (LGG) on rheumatoid arthritis (RA).Twenty-one RA patients were randomised to receive 2 capsules of LGG or a placebo twice daily in double-blind fashion for 12 months. Arthritis activity was evaluated by clinical examination, HAQ index, and laboratory tests (e.g. ESR, CRP, pro- and anti-inflammatory cytokines).There were no statistical differences in the clinical parameters, biochemical variables and HAQ index between the study groups over the intervention period. The mean number of tender and swollen joints decreased from 8.3 to 4.6 in the Lactobacillus group and from 5.5 to 4.8 in the placebo group (p = 0.41). According to the global assessment the RA activity was reduced in 71% (LGG group) vs. 30% (controls) (p = 0.15). Serum IL-1 beta increased slightly in the LGG group (p = 0.07), but no differences were seen in IL-6, TNF-alpha, MPO, IL-10 or 1L-12.Although there were no statistical significant differences in the activity of RA, more subjects in the LGG group reported subjective well being. More studies on the effects of probiotic bacteria in RA are needed.

Background The new 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis (RA) aim at earlier diagnosis of RA compared to the 1987 ACR criteria. Objective To evaluate the ability of the 2010 ACR/EULAR and the 1987 ACR classification criteria to predict radiographic progression after 10 years of follow-up. Methods All early arthritis patients referred to Central Hospital in Jyvaskyla from 1997 to 1999 (cases with peripheral joint synovitis, other specific diseases excluded) were included in this 10-year follow-up study. Radiographs of hands and feet were analysed according to Larsen on a scale of 0–100. Results At 10 years, 58% of the patients had an erosive disease (defined as Larsen ≥2 in at least one joint). The discriminative power of the 2010 ACR/EULAR and the 1987 ACR criteria (erosive disease at 10 years) were comparable, with area under the curve 0.72 (95% CI 0.65 to 0.79) (2010 ACR/EULAR criteria) and 0.65 (95% CI 0.58 to 0.72) (1987 ACR criteria). The respective sensitivities and specificities were 0.87 and 0.70, and 0.44 and 0.47. At 10 years, median (IQR) Larsen score was 6 (0, 15) among patients who had fulfilled both sets of criteria, 2 (0, 8) in those who met the 2010 ACR/EULAR and did not meet the ACR 1987 criteria, 0 (0, 5) in those who met ACR 1987 criteria but did not meet 2010 ACR/EULAR criteria, and 0 (0, 2) among patients who did not fulfil either of the criteria. The percentage of patients with erosions was 69%, 64%, 32% and 26%, respectively. Conclusions The ability of the 2010 ACR/EULAR and 1987 ACR classification criteria to identify erosive disease in early arthritis is low. The discriminative power of the 2010 ACR/EULAR criteria of erosiveness in 10 years is slightly better than that of the 1987 ACR criteria.

Objective To study the impacts of 1) the delay from the onset of symptoms to the institution of disease-modifying antirheumatic drug (DMARD) therapy, 2) two treatment strategies (treatment with a combination of DMARDs or with a single drug), and 3) the presence of HLA–DRB1 alleles (shared epitope) on the prediction of disease remission after 2 years in patients with early rheumatoid arthritis (RA). Methods In the FIN-RACo (FINnish Rheumatoid Arthritis Combination therapy) trial, 195 patients with recent-onset RA (median duration 6 months) were randomly assigned to receive either 1) a combination of DMARDs (sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone) or 2) a single DMARD with or without prednisolone. The presence of a shared epitope was tested for in 165 of the 178 patients completing the study. The additional variables of age, sex, presence of rheumatoid factor, number of fulfilled American College of Rheumatology criteria for the classification of RA, and length of delay from onset of symptoms to institution of therapy were entered into a logistic regression model to determine the significant predictors for remission at 2 years. Results The delay to therapy (cut point of 4 months) was the only significant predictor for remission in patients treated using the single-DMARD strategy, while no variable was a significant predictor for remission in those treated using the combination-DMARD strategy. The frequency of achieving remission in the combination-DMARD group after 2 years was similar in patients with short (0–4 months) and long (>4 months) delay periods (11 of 26 patients and 22 of 53 patients, respectively [∼42% in each group]), while the corresponding frequencies in the single-DMARD group were 8 of 23 patients (35%) and 7 of 63 patients (11%) (P = 0.021). The presence of a shared epitope was not related to the induction of remission. Conclusion The delay of a few months from the onset of symptoms to institution of therapy decreases the ability of the traditional single-drug strategy to induce remission in early RA.

Objective.With modern initial aggressive combination treatments with synthetic disease-modifying antirheumatic drugs (sDMARD), most patients with rheumatoid arthritis (RA) achieve remission, have marginal radiographic progression, and sustain normal function. Here we aim to identify the patients failing these targets even after aggressive treatment.Methods.Ninety-nine patients with early, active RA were treated with a combination of 3 sDMARD and prednisolone (PRD), and either infliximab or placebo infusions during the first 6 months, aiming at strict remission. After 24 months, the treatments became unrestricted. At 60 months, 4 evident clinical features of treatment failure were defined: area under curve (AUC) between 6–60 months for disease activity score assessing 28 joints > 2.6; AUC 6–60 for health assessment questionnaire > 0.5; progression in total Sharp/van der Heijde score 0–60 months > 3 units; and need of PRD or biologic DMARD treatment at 60 months.Results.A total of 93 patients were followed up for 60 months. Of them, 45 had no features of treatment failure, 30 had 1, 10 had 2, 7 had 3, and 1 patient had all 4 features. Having 2–4 features of treatment failure at 5 years was predicted by the health assessment score at baseline, and by even low residual disease activity at 3 and 6 months.Conclusions.Only 20% of the patients with RA treated early with combination sDMARD and PRD have more than 1 clinical feature of treatment failure at 60 months. Residual clinical disease activity at 3–6 months was the most important predictor for identifying these patients. The study was registered at www.clintrials.gov (NCT00908089).

An extensive drinking water-associated gastroenteritis outbreak took place in the town of Nokia in Southern Finland in 2007. 53% of the exposed came down with gastroenteritis and 7% had arthritis-like symptoms (joint swelling, redness, warmth or pain in movement) according to a population-based questionnaire study at 8 weeks after the incident. Campylobacter and norovirus were the main pathogens. A follow-up questionnaire study was carried out 15 months after the outbreak to evaluate the duration of gastrointestinal and joint symptoms. 323 residents of the original contaminated area were included. The response rate was 53%. Participants were inquired about having gastroenteritis during the outbreak and the duration of symptoms. Of those with gastroenteritis, 43% reported loose stools and abdominal pain or distension after the acute disease. The prevalence of symptoms declined promptly during the first 3 months but at 15 months, 11% reported continuing symptoms. 32% of the respondents with gastroenteritis reported subsequent arthritis-like symptoms. The disappearance of arthritis-like symptoms was more gradual and they levelled off only after 5 months. 19% showed symptoms at 15 months. Prolonged gastrointestinal symptoms correlated to prolonged arthritis-like symptoms. High proportion of respondents continued to have arthritis-like symptoms at 15 months after the epidemic. The gastrointestinal symptoms, instead, had declined to a low level. Public Library of Science open access

Ample evidence shows that both monitoring disease activity and aiming at remission,1–4 as well as using combinations of disease modifying antirheumatic drugs (DMARDs), are effective treatment strategies in early rheumatoid arthritis (RA).5–8 Still, some authorities stress the former, but ignore the latter.9 In the FIN-RACo trial, 195 patients with early, active RA were randomised for a 2-year treatment with either a triple-combination of DMARDs and prednisolone (FIN-RACo) or DMARD monotherapy and discretionary prednisolone (SINGLE); both drug treatment strategies aimed at strict remission.6 Thus, in case of active disease, all inflamed joints had to be injected with glucocorticoids and predefined DMARD treatment adjustments made. After 2 years, remission was more common in the FIN-RACo than in the SINGLE group (37% vs 18%), and in a multivariate analysis only the treatment strategy proved to predict remissions at 2 years.6 Further, at 5 years, work disability (WD) was less common in the FIN-RACo than in the SINGLE group, especially regarding the patients who had reached remission at 6 months.10 In these subanalyses we wanted to study separately the roles of targeted treatment and combination DMARD …

BACKGROUND Treatment of reactive arthritis (ReA) with antibiotics has so far remained controversial. Eradication of the causative microbe appears logical, but short term antibiotic treatment has no beneficial effect on the outcome of ReA. OBJECTIVE To evaluate the effect of a three month course of ciprofloxacin on ReA. METHODS In a randomised, double blind, placebo controlled trial, between December 1992 and February 1996, 71 patients with acute ReA triggered by a gastrointestinal or a urogenital infection were randomly assigned to receive ciprofloxacin 500 mg or placebo twice daily for three months. Patients were assessed at study entry, at 6 weeks, 3 months, 6 months, and 12 months. Sixty two patients were valid for the efficacy analysis. The primary outcome measures were erythrocyte sedimentation rate, number of swollen joints, patients self assessment, and complete recovery. RESULTS Adverse events were mostly mild and occurred in both treatment groups. There were no statistically significant differences in any of the primary or secondary efficacy variables between the study groups at baseline or during the 12 month follow up. All primary outcome measures indicated that the condition of the patients improved during the study. CONCLUSION Both groups tended to recover. Ciprofloxacin, given as a three month course, had no advantage over placebo treatment.

To ascertain the occurrence of renal involvement in patients with primary Sjögren's syndrome (pSS).Urinary total protein excretion from 24 h urine collection, as well as urinary excretion rates of albumin, alpha-1 microglobulin (alpha1m) and IgG from overnight 8 h collections, were determined from 78 pSS patients (75 females, three males). Urine acidification capacity after oral ammonium chloride load was tested in 55 of these patients.Mild proteinuria (0.15-0.42 g/24 h) was observed in 34 patients (44%). Increased urinary excretion rates of albumin (/=20 microgram/min), alpha1m (/=7.0 microgram/min) or IgG (/=5.0 microgram/min) were detected in nine (12%), nine (12%) and 11 patients (14%), respectively. Latent or overt distal renal tubular acidosis (dRTA) was observed in 18 out of 55 patients with pSS (33%). These patients had a longer duration of the disease (10+/-4 vs 8+/-4 yr; P/=0.05); they also had proteinuria (67 vs 27%; P/=0.025) and hypertension (44 vs 14%; P/=0.05) more frequently, and significantly higher serum creatinine (92+/-39 vs 78+/-13 micromol/l; P/=0.025) and serum beta-2 microglobulin (beta2m) levels (3.3+/-1.6 g/l vs 2.6+/-0. 6 g/l; P/=0.025) as compared to patients with normal urine acidification capacity.Inadequate renal acidification capacity, as well as mild proteinuria, were frequently found in patients with pSS. Those with dRTA had longer disease duration, a higher level of serum beta2m, and they had proteinuria and hypertension more frequently than those with normal renal acidification capacity.

OBJECTIVE To assess the prognosis of patients with sicca symptoms and to identify the clinical and immunological factors that most sensitively predict the later development of primary Sjogren’s syndrome (SS) or other connective tissue diseases. METHODS Eighty seven patients (72 female, 15 male) with sicca symptoms were re-evaluated after a median follow up time of 11 years (range 8–17). The clinical examination included ophthalmological examination (Schirmer’s test, break up time and Rose-Bengal staining). Labial salivary gland biopsy was performed and histological findings graded according to the Chisholm-Mason scale. The immunoserological tests included determination of rheumatoid factor (RF), antinuclear antibodies (ANA), anti-extractable nuclear antigen-antibodies (ENA), serum immunoglobulins IgA, IgG, and IgM, and serum β 2 -microglobulin (β 2 m). RESULTS At follow up 31 patients (36%) fulfilled modified Californian criteria (salivary flow measurements were not performed and Chisholm-Mason grades 3–4 were regarded as diagnostic histological findings) for possible or definite SS. Likewise, a significant progression of the histological findings was observed. Labial salivary gland re-biopsy was performed in 42 patients with grade 0–2 findings at baseline, progression to grades 3–4 being observed in 21 (50%) at follow up. The patients who later developed SS were at baseline significantly older (mean (SD) 52 (9) v 44 (14) years, p⩽0.005) compared with those not fulfilling the SS criteria at follow up; they also had significantly higher serum β 2 m (p⩽0.0005) and IgG concentrations (p⩽0.005), and they had positive ANA more frequently (p⩽0.01). CONCLUSION These results suggest that high age, increased values of serum β 2 m, ANA positivity and increased concentrations of serum IgG, might be useful indicators for the subsequent development of SS in patients with sicca symptoms. The prognosis of patients with these symptoms was favourable, and the clinical course was benign even in the 36% of patients who developed SS. No cases of lymphoma were observed.

Summary Background The treatment of rheumatoid arthritis should aim at clinical remission. This multicentre, randomised trial with 2-year follow-up sought evidence on the efficacy and tolerability of combination therapy (sulphasalazine, methotrexate, hydroxychloroquine, and prednisolone) compared with treatment with a single disease-modifying antirheumatic drug, with or without prednisolone, in the treatment of early rheumatoid arthritis. Methods 199 patients were randomly assigned to two treatment groups. 195 started the treatment (97 received combination and 98 single drug therapy). Single-drug therapy in all patients started with sulphasalazine; in 51 patients methotrexate was later substituted. Oral prednisolone was required by 63 patients. The primary outcome measure was induction of remission. Analyses were intention to treat. Findings 87 patients in the combination group and 91 in the single-therapy group completed the trial. After a year, remission was achieved in 24 of 97 patients with combination therapy, and 11 of 98 with single-drug therapy (p=0·011). The remission frequencies at 2 years were 36 of 97 and 18 of 98 (p=0·003). Clinical improvement (American College of Rheumatology criteria of 50% clinical response) was achieved after 1 year in 68 (75%) patients with combination therapy, and in 56 (60%) using single-drug therapy (p=0·028), while at the 2-year visit 69 and 57 respectively (71% vs 58%, p=0·058) had clinically improved. The frequencies of adverse events were similar in both treatment groups. Interpretation Combination therapy was better and not more hazardous than single treatment in induction of remission in early rheumatoid arthritis. The combination strategy as an initial therapy seems to increase the efficacy of the treatment in at least a proportion of patients with early rheumatoid arthritis.

Many autoimmune diseases occur concomitantly with celiac disease. We investigated prospectively the occurrence of celiac disease and small-bowel mucosal inflammation in patients with primary Sjögren's syndrome.A total of 34 patients with primary Sjögren's syndrome and 28 controls underwent small bowel biopsy. Villous morphology, jejunal intraepithelial lymphocytes, and mucosal HLA-DR were evaluated and DQA and DQB alleles, serum antiendomysial, and antigliadin antibodies were examined.Five (14.7%) of 34 Sjögren's syndrome patients were found to have celiac disease. The density of jejunal intraepithelial gammadelta+ T cells was increased in all celiac and in four nonceliac patients. All celiac patients, 69% of nonceliac Sjögren's syndrome patients, and 11% of control subjects showed enhanced HLA-DR expression (p0.001). HLA DQ2 was present in 19 (56%) patients with Sjögren's syndrome, including all five with celiac disease.The findings show a close association between Sjögren's syndrome and celiac disease. Even among nonceliac patients with primary Sjögren's syndrome, an ongoing inflammation is often present in the small bowel mucosa.

The aim of this study was to determine whether the +896 A→G substitution of the Toll-like receptor 4 ( TLR4 ) gene, causing the Asp299→Gly change in the extracellular domain of TLR4, influences treatment response in recent-onset rheumatoid arthritis. 169 patients with rheumatoid arthritis were genotyped from the Finnish Rheumatoid Arthritis Combination Therapy trial, in which they were treated either with only one disease-modifying antirheumatic drug (DMARD) with or without prednisolone (single group), or with three DMARDs and prednisolone (combination group). Patients homozygotic for the wild-type +896A allele were compared with those having the polymorphic G allele in terms of early clinical response (at 6 months) by the 28-joint Disease Activity Score (DAS28). 1 of 20 (5%; (95% (confidence interval (CI) 1 to 5)) patients of the single group with TLR4 +896AG or GG and 29 of 67 (43%; (95% CI 31 to 56)) patients with AA were in remission (p = 0.001). DAS28 of the single group with TLR4 +896AG or GG was higher than with AA (p = 0.019). In the combination group, remission rates and DAS28 values were comparable between the genotypes. The polymorphic TLR4 +896G allele may impair treatment response to single DMARD treatment in recent-onset rheumatoid arthritis.

The current treatment of rheumatoid arthritis (RA) aims at early and sustained remission.1 However, the opinions on how to reach this target vary. The European guideline recommends the use of initial methotrexate (MTX), and if that fails, adding a biologic. A combination of disease modifying antirheumatic drugs (DMARDs) is not seen as an option as initial therapy or as the next step in patients with active RA failing MTX.2 Others have, however, included combination DMARDs in the first and second line treatment recommendations,3 ,4 and the Finns, thanks to the encouraging results and comprehensive national participation in the FIN-RACo trial,5 even propose triple DMARD combination as the initial treatment in active early RA.6 Direct comparisons between combination therapy and single MTX have been lacking; until recently, the tREACH trial fulfilled this gap by confirming the superiority of triple combination compared with single MTX in early RA.7 The FIN-RACo trial proved that the initial triple DMARD combination (MTX, sulphasalazine (SASP) and hydroxychloroquine) is superior to single DMARD therapy, started with SASP, which, however, could be …

The present study was designed to compare peripheral blood neutrophil migration and leukotriene (LT) release between patients with rheumatoid arthritis (RA) and healthy controls and to correlate the neutrophil functions with clinical disease activity. Nineteen patients with moderately active RA and 19 age and sex matched healthy volunteers participated in this study. Isolated peripheral blood neutrophils from RA patients released equal amounts of LTB4 but their random migration was enhanced as compared with neutrophils from healthy controls. LTB4 release in whole blood was significantly lower in samples from RA patients than in those from the healthy volunteers (13.5 +/- 1.4 and 19.1 +/- 1.4 ng/10(6) neutrophils respectively; P < 0.001). LTB4 release from isolated RA neutrophils correlated with the levels of C-reactive protein, duration of morning stiffness and Ritchie articular swelling index. Concentrations of hyaluronate, cyclic AMP and 13, 14-dihydro-15-keto prostaglandin were not different between patients with RA and healthy volunteers. Neither was there any difference in TXB2 production by platelets during blood clotting. In conclusion, peripheral blood neutrophils of RA patients seem to be primed and/or activated as their random migration is enhanced as compared with those of healthy volunteers. In RA, LTB4 release from peripheral blood neutrophils seems to reflect the clinical activity of the disease. However, RA neutrophils released smaller (in whole blood) or equal (isolated cells) amount of LTB4 as compared with the respective controls. These contradictory findings suggest that LTB4 release from peripheral blood neutrophils has no major role in the regulation of disease activity in rheumatoid arthritis.

To study the role of different seasons in the disease activity of patients with systemic lupus erythematosus (SLE). Additionally, to evaluate whether the outdoor behaviour during the summer or a photoprovocation test affects disease activity.33 patients with SLE were examined by a rheumatologist and a dermatologist at a university hospital in winter, spring, and summer. The activity of SLE was assessed by the ECLAM index. Their outdoor behaviour was recorded by a questionnaire during the summer. In the winter, 12 patients were photoprovoked by ultraviolet A and B radiation on a small skin area.The ECLAM scores were higher in spring and tended to be higher in summer than in winter (p = 0.006 and p = 0.051). This finding, as well as the outdoor behaviour, were independent of the patients' own impression of their photosensitivity. Overall, the sun protection actions were inadequate. The photoprovocation had no statistical effect on disease activity, but one patient had a violent exacerbation of SLE manifestations shortly after the photoprovocation.In the northern climate SLE may be activated during the sunny season. Therefore, more effort should be focused on sun protection of patients with SLE.

To evaluate pulmonary findings in patients with primary Sjögren's syndrome (SS).Prospective data collection.Seventeen consecutive nonsmoking patients with primary SS.Mild radiologic parenchymal changes were seen in two patients. Pulmonary hyperinflation (residual volume/total lung capacity [RV/TLC] percent ratio measured minus [-] RV/TLC percent ratio predictedor = 8) was observed in 9 (53%) patients, whereas obstructive and restrictive changes were infrequently found in ordinary spirometry (FVC, FEV1, FEV%) (none and two cases, respectively). Patients with SS with hyperinflation had significantly lower maximal expiratory flow MEF50 (p0.05), MEF25 (p0.05), and higher total lung capacity (p0.05) and FRC (p0.05) values as compared with those patients with SS without hyperinflation. They were also more frequently dyspnoeic (six vs none, p0.02) and had higher mean serum beta 2-microglobulin levels (3.6 +/- 1.0 mg/L vs 2.6 +/- 0.7 mg/L, p0.025). The levels of serum beta 2-microglobulin correlated inversely with FVC (r = - 0.583, p0.01), FEV1 (r = - 0.533, p0.05), diffusing capacity for carbon monoxide (r = - 0.580, p0.01); its correlation with RV/TLC percent ratio was positive and relatively significant (r = 0.447, 0.05p0.10).Pulmonary hyperinflation associated with diminished peripheral spirometric flow values is frequently found in patients with primary SS. This together with the correlation of disturbed lung function parameters to elevated serum beta 2-microglobulin levels suggests that lungs and especially small airways may be an usual target organ in primary SS.

Objective. To evaluate renal biopsy findings and clinicopathologic correlations in patients with rheumatoid arthritis (RA). Methods. Retrospective study of renal biopsy specimens from 110 RA patients in whom the clinical renal disease was probably due to RA itself and/or to antirheumatic therapy. Results. The most common histopathologic finding was mesangial glomerulonephritis (GN) (n = 40), followed by amyloidosis (n = 33), membranous GN (n = 19), focal proliferative GN (n = 4), minimal-change nephropathy (n = 3), and acute interstitial nephritis (n = 1). Amyloidosis was the most common finding in patients with the nephrotic syndrome. In patients with isolated proteinuria, amyloidosis, membranous GN, and mesangial GN were almost equally common. Although mesangial GN was found in almost two-thirds of the RA patients with hematuria (with or without proteinuria), there still remained a 1 in 5 chance that the biopsy would reveal membranous GN or amyloidosis. Membranous GN was closely related to gold or D-penicillamine therapies, whereas mesangial GN probably related to RA itself. Conclusion. The renal morphologic lesion in RA patients with isolated proteinuria and those with hematuria cannot be accurately predicted on the basis of clinical symptoms and signs. Biopsy is thus useful in differential diagnosis, assessment of prognosis, and decision-making with regard to treatment.

Estimation of the glomerular filtration rate (GFR) is the most widely used test of renal function, reflecting the relative mass of functional renal tissue and thus the number of functioning nephrons. Methods based on measurement of exogenous substances such as inulin, 51Cr-EDTA, 99mTc-diethylenetriaminepentaacetic acid, and iohexol are accurate but too complex and laborious for routine clinical use; thus, measurement of endogenous blood substances is common practice. Plasma or serum creatinine and its renal clearance are the approaches most commonly used despite their acknowledged unreliability. Cystatin C, a small basic protein, has been proposed as a better marker than creatinine. Recently, the value of cystatin C was thoroughly reviewed in this Journal (1), and according to this review and a new metaanalysis (2), most studies have concluded that cystatin C is superior to plasma creatinine, whereas several authors have concluded that cystatin C provides no advantage. One purpose of the present study was to clarify possible reasons for the earlier, partly conflicting results. A recently published guideline from the National Kidney Foundation (3) recommended that GFR be estimated from prediction equations taking into account the serum creatinine concentration and some or all of the following variables: age, gender, race, and body size. We therefore also compared cystatin C with GFRs calculated by the Cockcroft–Gault (4) and the MDRD(5) formulas. We studied 112 patients (55 men and 57 women) for whom 51Cr-EDTA clearance had been requested. The mean age of the patients was 57.0 years (range, 17–89 years). Body mass index (BMI) was 15.2–42.4 kg/m2, and 51 …