Tissue-derived macromolecules and markers of inflammation in serum in early rheumatoid arthritis: relationship to development of joint destruction in hands and feet

We have previously shown that serum concentrations of cartilage oligomeric matrix protein (COMP) are increased early in rheumatoid arthritis (RA) patients who subsequently develop advanced large-joint destruction. A prognostic value for joint damage of serum concentrations of hyaluronan (HA) is also suggested by previous studies. In contrast, serum concentrations of bone sialoprotein (BSP) have not been useful for identifying patients with progressive large-joint destruction. In the present study, we have examined the hypothesis that serum concentrations of these tissue-derived markers are of prognostic value in RA for the development of radiographically detectable joint damage in hands and feet. Serum concentrations of COMP, HA and BSP were quantified in samples obtained from 62 patients within the first year after onset of RA and were related to the development of radiographically detectable damage in these joints after 5 yr. Neither the serum concentrations of COMP nor of BSP at inclusion predicted joint damage in hands and feet after 5 yr, and the concentration of these proteins did not change over the 5 yr period. However, the serum concentration of HA at inclusion correlated with the radiographic score at the 5 yr follow-up (r = 0.425, P < 0.01), but was not a better predictor in this respect than the erythrocyte sedimentation rate or C-reactive protein levels at inclusion. Thus, serum concentrations of the three studied tissue-derived macromolecules were in this study not useful for identifying patients prone to small-joint destruction.     

Assessment of disease activity in rheumatoid arthritis using magnetic resonance imaging: quantification of pannus volume in the hands

We attempted to assess whether pannus volume measured by magnetic resonance imaging (MRI) can be used as an indicator of disease activity in rheumatoid arthritis (RA). Eleven women (mean age 46 yr) with uncontrolled RA were studied for 1 yr. Pannus formation in both hands was quantified using MRI at the start of the study, and at 6 and 12 months thereafter. The volume of enhancing pannus (VEP) was compared with changes in the radiological scores, grip strength, joint tenderness counts, joint swelling counts, erythrocyte sedimentation rate (ESR), and serum C-reactive protein (CRP). Patients were classified into three groups based on VEP changes between 0 and 12 months: unchanged (n = 2), decreased (n = 6) and increased (n = 3). VEP at 6 months and at 12 months differed significantly between the three groups. No statistically significant differences were found between the groups in radiographic scores, physical parameters or laboratory parameters despite the fact that some of these parameters changed in the direction indicated by the changes in VEP. VEP can be used as a new indicator to assess disease activity in individual RA patients and, using this parameter, treatment outcome can be assessed in fewer subjects than with traditional measures.     

Reference curves of radiographic damage in patients with rheumatoid arthritis: application of quantile regression and fractional polynomials

OBJECTIVE: To (1) introduce the methodology of quantile regression and fractional polynomials; (2) test the application of this methodology to develop, conditional on disease duration, preliminary reference curves of radiographic damage in patients with rheumatoid arthritis (RA); and (3) prove the importance of the definition and selection of the reference group when developing reference curves. METHODS: The study design was cross sectional. The main study factors were disease duration and radiographic damage using the Larsen score. The 2 study samples were 98 patients from a multicenter trial of cyclosporine and 203 patients with RA from a teaching hospital clinic. RESULTS: Using disease duration as the time dependent covariate we constructed quantile regression reference curves of radiographic damage. The reference curves for the 2 samples differed in shape, location, and slope. CONCLUSION: Quantile regression and fractional polynomials simplify the construction of reference curves when data cannot be easily modified to meet assumptions of normality, linearity, and constant variance. Quantile reference curves provide clinicians with a useful clinical tool to measure outcome at arbitrary timepoints, to interpret change, and to set treatment objectives. However, the definition and selection of the reference used to construct the reference curves is of critical importance.     

Only high disease activity and positive rheumatoid factor indicate poor prognosis in patients with early rheumatoid arthritis treated with "sawtooth" strategy

OBJECTIVES: To investigate the prognostic significance of clinical and genetic markers on the outcome of patients with recent-onset rheumatoid arthritis (RA) treated actively with slow acting antirheumatic drugs (SAARDs). METHODS: A total of 142 consecutive patients with early RA (median disease duration of 7 months) were treated according to the "sawtooth" strategy and prospectively followed up for an average of 6.2 years. Several clinical parameters at start as well as genetic markers were related to the functional outcome (ARA Functional class and HAQ disability score) and radiographic joint damage (Larsen's score) at the latest visit. RESULTS: In logistic regression analysis only Mallya score (including morning stiffness, pain scale, grip strength, Ritchie's articular index, haemoglobin, and erythrocyte sedimentation rate) at baseline, and Mallya score and rheumatoid factor (RF) positivity at one year were found to be of significance with respect to the radiographic outcome of the patients. Furthermore, at the latest visit HAQ score was related to radiographic score. At baseline the mean ages of the DR4 positive patients and the patients with RA associated DR alleles were statistically significantly lower than those without the above mentioned risk factors (44 v 49, p = 0.03 and 41 v 53, p = 0.04, respectively). However, these genetic markers had no prognostic significance on the functional or radiographic outcome of the patients. CONCLUSION: High clinical disease activity at baseline and RF positivity especially at one year after the institution of SAARD treatment are the best predictors of poor prognosis in early RA. However, from the clinical point of view, the disease outcome of an individual patient with early RA, cannot be predicted accurately enough by present means.     

Effect of valued activity disability, social comparisons, and satisfaction with ability on depressive symptoms in rheumatoid arthritis.

This longitudinal study identified a model through which function affects the psychological well-being of individuals with rheumatoid arthritis (RA). Results of hierarchical linear regression analyses (N = 436) demonstrated that greater physical impairment resulted in greater disability in valued activities and engagement in unfavorable social comparisons. All 3 factors--greater physical impairment, greater disability in valued activities, and unfavorable comparison evaluations--predicted low satisfaction with abilities. Low satisfaction with abilities was the most important predictor of higher depressive symptoms and mediated the impact of physical impairment, valued activity disability, and unfavorable comparisons on depressive symptoms. Results highlight the role of personal meaning attached to changes in functional status in predicting the long-term psychological well-being of individuals with chronic illnesses such as RA. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interpersonal stress, depression, and disease activity in rheumatoid arthritis and osteoarthritis patients

The relationships among interpersonal stressors, depression, coping inefficiency, hormones (prolactin, cortisol, and estradiol), and disease activity were examined. The sample comprised 33 women with rheumatoid arthritis (RAs; age 37-78) and 37 women with osteoarthritis (OAs; age 47-91), who served as controls. In a regression analysis, interpersonal conflict events accounted for more than twice as much variance in depression in RAs than in OAs. In the RA patients, the immune-stimulating hormones prolactin and estradiol were significantly positively correlated with interpersonal conflicts, depression, coping inefficacy, and clinician ratings of disease activity, suggesting that RAs are more reactive to interpersonal stressors than are OAs, both psychologically and physiologically.     

Elderly rheumatoid arthritis patients on steroid treatment tolerate physical training without an increase in disease activity

The effects of physical training on elderly, fragile patients with rheumatoid arthritis (RA) who are on low-dose steroids were investigated. The controlled study included 24 patients who had been treated with low-dose steroids for 2 years. Each patient was assigned either to a treatment group receiving training or to an untrained control group. The training took place over a 3-month period and was based on a protocol using progressive interval training consisting of bicycle exercises, heel lifts, and step-climbing. The exercises were performed twice weekly for 45 minutes. Comparison of the two groups showed that disease activity did not increase in the trained group and that fewer, but not significantly fewer, swollen joints were observed in this group (p = 0.06). No significant changes were noticed in erythrocyte sedimentation rate, tender joints, or morning stiffness. The work capacity of the trained patients were doubled and the numbers of repetitions increased 76%. Individually adapted exercise programs can therefore be recommended for elderly rheumatoid arthritis patients on steroid treatment.     

Life events and disability in rheumatoid arthritis: a European cohort

The objective was to study the relationship between life events (LE) and the clinical status of patients suffering from recently diagnosed rheumatoid arthritis (RA) in a 2 yr follow-up. As part of a multicentre European cohort study, 370 French and Dutch patients were questioned three times at 1 yr intervals about LE which had occurred in the previous year. Three criteria were used to quantify the degree of disease activity (Ritchie's index), the level of functional disability [Health Assessment Questionnaire (HAQ)] and perceived health [Overall Evaluation of Health (OEH)]. Total LE and desirable LE showed a weak negative correlation with the HAQ scores. On the other hand, death-related LE did not seem to modify patient status. The higher the number of health-associated LE, the greater the deterioration in HAQ and OEH scores. The results indicate that LE do not affect the course of early RA in a spectacular manner.     

Bronchiolitis obliterans and no radiographic abnormalities in a patient with rheumatoid arthritis

In a case-control study, we evaluated the association of the risk of menstrual disorders with four periconceptional factors: short preceding interpregnancy interval (< 6 months), low (< or = 19 years) or high (> or = 40 years) maternal age at conception, and month of conception. We divided 919 women who had visited a fertility clinic between 1991 and 1995 into three categories: cases (with mean menstrual cycle length > or = 42 or < or = 21 days, or a variation of > or = 14 days between cycles, or amenorrhea, N = 294), controls (with cycles within a range of 25-35 days and variation < or = 7 days, N = 520), and intermediates (N = 105). A self-administrable questionnaire was mailed, asking for information about maternal reproductive history and age, and potential confounders such as smoking, exercise, and level of education. Response (77%) differed little among cases, intermediates, and controls. We found elevated risks for short pregnancy intervals [adjusted odds ratio (OR) = 2.04; 95% confidence interval (CI) = 1.04-4.02] and advanced maternal age (OR = 3.24; 95% CI = 1.27-8.30) but not for low maternal age (OR = 0.58; 95% CI = 0.11-3.14) (cases vs controls). We found similar effects for intermediates vs controls. The distribution of month of conception did not differ much from controls for both cases and intermediates. The results indicate that conception after short pregnancy intervals or at advanced maternal age increases the risk of menstrual disorders in daughters. The precise etiology is unclear, but it may lie in the quality of the oocyte at conception.     

Clinical course and remission rate in patients with early rheumatoid arthritis: relationship to outcome after 5 years

OBJECTIVE: To investigate the clinical course in early rheumatoid arthritis (RA) patients followed prospectively, to relate course to outcome after 5 yr, and to try to identify prognostic features. METHODS: A total of 183 patients with definite RA and a mean disease duration of 11 months were included. Of these, 75% were rheumatoid factor (RF) positive; 85% carried the shared epitope, 32% on both alleles. Most patients were assessed every 6 months. Disability was evaluated with the Health Assessment Questionnaire (HAQ) and radiographic findings according to Larsen. Remission was defined in two ways: with the American Rheumatism Association (ARA) criteria and as 'no arthritis at least at one follow-up visit'. RESULTS: Twenty per cent achieved ARA-defined remission periods of at least 6 months duration; 21 were spontaneous and 18 drug induced. Average length of remission was 20.5 months. The remission periods constituted 7% of follow-up for all patients. Another 36% achieved remission according to the second definition. All 56% were considered to have a relapsing-remitting disease pattern, in contrast to the remaining 44% with a persistent disease pattern. More patients with persistent disease were treated with disease-modifying anti-rheumatic drugs (DMARDs) and had also received a larger number of different drugs. Outcome after 5 yr regarding disability, joint inflammation and joint damage was worse for patients with persistent disease. Neither ARA-defined remission nor disease pattern could be accurately predicted. CONCLUSIONS: Long-term ARA-defined remission was rare, constituting 7% of follow-up for the entire cohort. For those 20% achieving remission, this period represented 34% of their follow-up. A total of 56% had a relapsing-remitting disease pattern and 44% had a persistent disease pattern. This classification had prognostic implications with persistency being a bad prognostic sign.     

Fatigue in HIV illness: relationship to depression, physical limitations, and disability

Several filters specific for respiratory function tests have been on the market for several years. Recommended by the manufacturers to avoid contaminating the equipment and thus improve patient safety, these filters require a considerable financial investment. We studied the passage of diluted blood into artificial saliva in a patient model simulating inspiration tests and rapid forced expiration to assess the retention capacity of three filters used for respiratory function tests: Multi SPIRO MI-90016 (MultiSPIRO), PF 30S (Pall Biomedical) and Spirobac (Dar. S.p.A). The mean percentage of passage was 1.48% through the MI-90016 filter, 57.15% through the PF 30 S filter and 70.45% through the Spirobac filter. These findings provide further elements for choosing filters for respiratory function tests. Indeed, despite the manufacturers' commercial arguments, the technical documents provided do not give necessary information on the filtering capacity of the filters on the market. We have observed that two out of the three filters tested do no meet the standards expected by clinicians.     

Plasminogen activation in synovial tissues: differences between normal, osteoarthritis, and rheumatoid arthritis joints

OBJECTIVE: To analyse the functional activity of the plasminogen activators urokinase (uPA) and tissue type plasminogen activator (tPA) in human synovial membrane, and to compare the pattern of expression between normal, osteoarthritic, and rheumatoid synovium. The molecular mechanisms underlying differences in PA activities between normal and pathological synovial tissues have been further examined. METHODS: Synovial membranes from seven normal (N) subjects, 14 osteoarthritis (OA), and 10 rheumatoid arthritis (RA) patients were analysed for plasminogen activator activity by conventional zymography and in situ zymography on tissue sections. The tissue distribution of uPA, tPA, uPA receptor (uPAR), and plasminogen activator inhibitor type-1 (PAI-1) was studied by immunohistochemistry. uPA, tPA, uPAR, and PAI-1 mRNA values and mRNA distribution were assessed by northern blot and in situ hybridisations respectively. RESULTS: All normal and most OA synovial tissues expressed predominantly tPA catalysed proteolytic activity mainly associated to the synovial vasculature. In some OA, tPA activity was expressed together with variable amounts of uPA mediated activity. By contrast, most RA synovial tissues exhibited considerably increased uPA activity over the proliferative lining areas, while tPA activity was reduced when compared with N and OA synovial tissues. This increase in uPA activity was associated with increased levels of uPA antigen and its corresponding mRNA, which were localised over the synovial proliferative lining areas. In addition, in RA tissues, expression of the specific uPA receptor (uPAR) and of the plasminogen activator inhibitor-type 1     

Depression and the long-term risk of pain, fatigue, and disability in patients with rheumatoid arthritis

OBJECTIVE: To determine whether a previous episode of major depression leaves a "scar" that places previously depressed patients with rheumatoid arthritis (RA) at risk for experiencing high levels of pain, fatigue, and disability. METHODS: A cohort of 203 patients with RA was randomly selected from a national panel and interviewed by phone about pain, fatigue, depressive symptoms, disability, and history of major depression. RESULTS: Excluding patients who met the criteria for current major depression, patients with both a history of depression and many depressive symptoms at the time of the interview (dysphoria) reported more pain than those without current dysphoria, irrespective of whether they had a history of depression. Dysphoria alone was not reliably related to pain reports. CONCLUSION: An episode of major depression, even if it occurs prior to the onset of RA, leaves patients at risk for higher levels of pain when depressive symptoms persist, even years after the depressive episode.     

Cognitive distortion in rheumatoid arthritis: Relation to depression and disability.

Rheumatoid arthritis (RA) is often accompanied by significant levels of depression and disability. Previous research has demonstrated that cognitive distortions are related to depression and disability in other chronic pain conditions. Our study tested the relevance of Beck's model to RA by examining the relation between cognitive distortion, as measured by the Cognitive Error Questionnaire, and both self-reported and interview-rated depression and disability in 92 RA patients. Even when disease severity was controlled, cognitive distortion was significantly associated with depression. Although cognitive distortion was also related to physical disability, this relation was smaller. The results are discussed in terms of the potential relevance of Beck's model to the treatment of depression and disability in RA patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Amyloidosis--incidence and early risk factors in patients with rheumatoid arthritis

In a 15-year follow-up examination, reactive secondary amyloidosis (RSA) was found by subcutaneous fat biopsy in six out of 74 still living patients (8.1%) of an original population of 102 with erosive and seropositive rheumatoid arthritis (RA). Five of the 24 deceased patients had had RSA. Thus the 15-year incidence of RSA in RA was at least 10.9% (11/102). To study early prognostic aspects of RSA, comparison was made of 14 entry variables and the initial treatment in the RSA group (n = 11) and the control group (n = 81) respectively. At onset (< or = 6 months) of RA only serum orosomucoid, but after three years morning stiffness, ESR, serum CRP and orosomucoid were significantly worse in patients whom later developed RSA. Three out of 48 patients treated with gold sodium thiomalate and seven out of 30 treated with chloroquine developed RSA (p = 0.04). It is concluded that continuously active disease was the risk factor underlying RSA. The role of early chloroquine therapy is discussed.     

Activation of the haemostatic system in children with juvenile rheumatoid arthritis correlates with disease activity

Twenty-four children with juvenile rheumatoid arthritis (JRA) and 10 children with postinfectious arthropathies were investigated for markers of blood coagulation and fibrinolytic activity: Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), and D-Dimer were measured using solid phase enzyme linked immunosorbent assays (ELISA). Results were compared with clinical and conventional laboratory signs of disease activity. F1+2, TAT, D-Dimer, and fibrinogen were significantly elevated in children with JRA as compared with healthy children and children with postinfectious arthropathies. F1+2, TAT, and D-Dimer correlated significantly with disease activity, assessed by determination of the joint index score and C-reactive protein (CRP). The study demonstrates a subclinical activation of the haemostatic system in children with JRA correlating with disease activity, which might be caused by the action of several immunomediators on cells (monocytes, endothelial cells) playing a role in the regulation of blood coagulation activity.