Kerstin Eberhardt

Course of radiographic damage over 10 years in a cohort with early rheumatoid arthritis

Objective: To investigate development of radiographic damage in hands and feet of patients with early rheumatoid arthritis (RA) monitored prospectively for 10 years, and to search for prognostic factors. Patients and methods: 181 patients with early RA (mean disease duration one year) were assessed annually with radiographs of hands and feet during years 0–5 and at year 10. Radiographs were evaluated according to Larsen (range 0–200). Predictive factors for progressive disease for years 0–5 and 5–10 were evaluated by logistic regression analyses. Results: 82/168 (49%) patients had erosions at inclusion and almost all became erosive with time (90% after two years and 96% after 10 years). Radiographic progression was most rapid during the first two years and 75% of all damage occurred during the first five years. The median Larsen score increased from 6 at inclusion to 41 after five years and 54 after 10 years. Only 5.3% of all evaluated joints became maximally eroded, the second metacarpophalangeal joint being the most commonly affected. Mean ESR during the first three months and rheumatoid factor status were significant predictors for radiographic progressive disease, it was not possible to predict non-progressive disease. Conclusions: Joint damage in hands and feet developed early and progression was most rapid during the first years of disease. The different rates of progression at different stages should be considered in the design of trials of drugs aimed at retarding joint damage. Disease activity at study start influenced the degree of joint damage during the entire 10 years.

Ten year outcome in a cohort of patients with early rheumatoid arthritis: health status, disease process, and damage

Objective: To investigate outcome as measured by health status, disease process, and damage in an unselected group of patients with early rheumatoid arthritis (RA) monitored prospectively for 10 years and to search for prognostic factors. Patients and methods: 183 patients with RA with disease duration <2 years were assessed annually at a team care unit. Health status was measured by the Health Assessment Questionnaire (HAQ) and functional class. Disease process was assessed by clinical and laboratory measures of disease activity and evaluation of disease course. Damage was quantified as occurrence of major extra-articular manifestations and need for large joint replacements. Possible predictive factors were evaluated by logistic regression analyses. Results: 168/183 patients completed the entire follow up period. Of all 183 patients, 137 (75%) had been treated with disease modifying antirheumatic drugs and 84 (46%) with low dose oral glucocorticoids. After 10 years 158 patients (94%) managed daily life activities independently (functional class I–II). As measured by the HAQ 20% had almost no disability, 28% were mildly disabled, and 10% were seriously disabled. Median HAQ score had increased from 0.8 to 1.1 (p<0.001). Disease activity was significantly reduced. 133 patients (79%) had a relapsing remitting disease course and 30 patients (18%) were in remission as defined by the American College of Rheumatology criteria. Thirty patients (17%) had undergone large joint replacements. Fifteen patients (8%) had developed major extra-articular complications. The HAQ score during the first three months predicted disability at 10 years with an odds ratio of 13.4. Conclusions: Prospective studies such as this give important knowledge of the variable long term prognosis of RA and provide necessary background information for clinical trials of new treatment modalities.

Mortality in rheumatoid arthritis patients with disease onset in the 1980s

OBJECTIVE Several previous studies have shown increased mortality in rheumatoid arthritis (RA) patients. This study investigated if this was true also for patients with disease onset in the 1980s. PATIENTS AND METHODS The study group comprised 183 patients (67 men and 116 women) with definite RA participating in an ongoing prospective study. Mean age at onset of disease was 51 years, and mean duration of joint symptoms at inclusion was 11 months. The patients were included between 1985–89. Seventy five per cent of the patients were rheumatoid factor (RF) positive, 85% carried the shared epitope, and 90% became erosive. By 1 September 1997 the number and causes of death, obtained from the death certificates, were recorded. Standardised mortality ratio (SMR) was calculated, comparing the observed number of deaths in the cohort with the expected number of deaths in the general population in the same area, age and sex matched. The predictive values of demographics, genotype, RF status, and clinical data at baseline were estimated using the Cox proportional hazards regression model. RESULTS Eighteen patients (11 men and 7 women) had died compared with 20 expected deaths. SMR with 95% confidence intervals was 87 (53, 136). There was no significant increase in the number of deaths at any time during follow up for either sex. RA was not the main cause of death in any of the cases. By reading the patient charts two cases were found where RA or its treatment could have contributed to death. No RA related variable contributed significantly to an increased risk of death. CONCLUSION There was no increased mortality during the first 8–13 years of disease in this group of patients who developed RA in the 1980s.

Associations of HLA-DRB and HLA-DRQ genes with two and five year outcomes in rheumatoid arthritis.

OBJECTIVE--To evaluate the clinical usefulness of genomic HLA typing during the first five years of established rheumatoid arthritis (RA). METHODS--The HLA-DRB and -DQB alleles were determined by restriction length polymorphisms and polymerase chain reaction amplification with sequence specific primers in 99 Swedish patients with RA. Clinical features after two and five years disease duration were related to the genetic pattern. Seventy four patients were seropositive, 25 had nodules, 90 developed erosions, and 15 required joint replacements. Twelve patients were in remission after five years. Disability was assessed by health assessment questionnaire, and radiographic damage in hands and feet by the Larsen method. RESULTS--Eighty seven per cent of the patients carried the conserved third hypervariable region sequence (HVR3), 32% had DRB1*04 on one allele, and 26% had DRB1*04 on both alleles (all frequencies significantly greater than in controls). Frequencies of DRB1*04 associated DQB*0301 and *0302 were normal. Patients carrying DRB1*04 on both alleles tended to have more radiographic changes after two years, but this difference had diminished after five years. Disability did not vary with regard to the genotype. Homozygous HVR3 patients had about three times greater risk of undergoing joint replacement. Homozygosity for HVR3 and presence of DQB*0302 both tended to be associated with erosive disease. CONCLUSIONS--We confirmed a strong association of disease with the presence of the shared epitope on one or two alleles. However, genotype was not strongly associated with disease severity after two and five years disease duration, and thus the value of genomic typing to select patients for early aggressive therapy is questionable.

Early Rheumatoid Arthritis – some Social, Economical, and Psychological Aspects

Physical, psychological, and social features were assessed with standardized methods in 84 early RA patients followed prospectively for 2 years. During this time disease activity decreased, and disability evaluated by HAQ remained small. Psychological distress measured by SCL-90 (Symptom Check List) was in general not very pronounced and fairly stable over time. A high pain level at baseline provided a 4 times higher risk for a high level of psychological distress after 2 years. The prevalence of early retirement was 37% at the end of the study. Physical demanding work and a high initial HAQ score were the best predictors of work disability, increasing the risk of not working 10.7 and 5.5 times, respectively. At least 28% of patients had lower annual income compared to the year before disease onset. The ability to do shopping, home work, leisure time activities and social activities were negatively influenced by the disease in more than half of the patients. The social and economical consequences were thus considerable in the early stages of RA.

Orthopaedic surgery in patients with rheumatoid arthritis over 20 years: prevalence and predictive factors of large joint replacement

Objective: To study the prevalence of orthopaedic surgery and to evaluate possible predictive factors for large joint replacements in patients with early rheumatoid arthritis (RA). Patients and methods: A cohort of 183 patients (116 (63.4%) female) with early RA was monitored for 16–20 years after recruitment during 1985–9. Mean (SD) age of patients 51.4 (12.4) years; mean (SD) duration of symptoms before inclusion 12 (7) months and mean (SD) duration of follow-up 16 (4) years. Occurrence of orthopaedic surgery was recorded continuously. A first prosthesis of a large joint (shoulder, elbow, wrist, hip, knee or ankle) was used as outcome variable in the predictive analyses. Results: In total, 386 orthopaedic interventions were performed in 106/183 (58%) patients during follow-up and a large joint replacement was performed in 44/183 (24%) patients. Using a Cox regression model, it was shown that Health Assessment Questionnaire, C-reactive protein and erythrocyte sedimentation rate at inclusion, and radiographic changes in small joints after 1 year, were associated with an increased risk of receiving prosthesis of large joints. Conclusion: In this cohort of patients with RA monitored from early disease stage, orthopaedic surgical procedures were performed in more than half of the patients. This included first large joint replacements in 24% of the cases. Easily available measures were identified as predictors of such joint replacements. This study could serve as a reference for comparison with cohorts of patients with RA recruited today, in which new more efficacious treatments are used.

Circulating soluble E-selectin in early rheumatoid arthritis: a prospective five year study

Background: Soluble E-selectin (sE-selectin) is a marker of activation of vascular endothelium. Objective: To examine serum levels of sE-selectin in a cohort of 85 patients with early rheumatoid arthritis (RA) followed up for five years. Methods: sE-selectin levels were assessed annually using an enzyme linked immunosorbent assay (ELISA) and related to simultaneously obtained clinical and laboratory measures. Joint inflammation was evaluated by active joint count, functional status by Health Assessment Questionnaire (HAQ), and radiographic findings in hands and feet by the Larsen method. Laboratory tests included serum C reactive protein (CRP) level, erythrocyte sedimentation rate, blood haemoglobin level, white blood cell count (WBC), and platelet count. Area under the curve (AUC) was calculated for each variable, and Jonckheeres test for ordered alternatives was applied to assess significance of association between sE-selectin AUC tertiles and other variables. Baseline sE-selectin tertiles were related to change in Larsen score and HAQ score at five years. Odds ratios (OR) with 95% confidence interval (CI) were calculated using univariate and multivariate logistic regression. Results: sE-selectin levels were associated with CRP level (p=0.012), WBC (p=0.037), active joint count (p=0.019), progression of joint destruction (p=0.038), and HAQ score at five years (p=0.021), but not with extra-articular symptoms or comorbidity. Baseline sE-selectin levels in the third tertile predicted the HAQ score at five years (OR 4.18, 95% CI 1.15 to 15.22). sE-selectin levels of patients did not differ significantly from those of healthy control subjects. Conclusion: The degree of activation of vascular endothelium is associated with activity and outcome of early RA.

Disease activity and joint damage progression in early rheumatoid arthritis: relation to IgG, IgA, and IgM rheumatoid factor.

The clinical and biochemical correlations with joint damage progression over two years in a consecutive group of 68 patients with rheumatoid arthritis with disease duration of less than two years are reported. Joint damage was assessed with Larsens severity scale and a measure of change in progression rate constructed. Initial haemoglobin concentration, Ritchie index, and Waaler-Rose titre in combination accounted for one third of the variance in joint damage progression. Rheumatoid factor (RF) concentrations were followed with enzyme linked immunosorbent assays (ELISAs) for IgG RF, IgA RF, and IgM RF. The RF concentrations, except IgG RF, decreased with time; significant correlations between RFs and disease activity were few and barely clinically useful. After two years IgG RF correlated significantly with a radiological score if early non-erosive changes were omitted. All RFs tended to correlate better with this radiological score at all three observation points. Analyses of the change in progression rate indicated a time delay between development of radiographic changes and increase of IgG RF. These results suggest an indirect relation between RFs and joint damage. Clinical and biochemical improvements in early RA occur despite joint damage progression, and conventional markers have insufficient predictive value.

A longitudinal follow‐up of hand involvement and activities of daily living in early systemic sclerosis

Objective: To investigate the development of hand involvement and activities of daily life (ADL) in early systemic sclerosis (SSc), and to examine the usefulness of the Hand Mobility in Scleroderma (HAMIS) test in a longitudinal study. Methods: Forty‐three patients with disease duration no longer than 3 years and at least 4 years of follow‐up formed the study group. Based on skin involvement, 31 patients were classified as limited cutaneous SSc (lcSSc) and 12 as diffuse cutaneous SSc (dcSSc). The patients were assessed regarding hand function [mobility (HAMIS), grip force (Grippit), and self‐assessed hand function visual analogue scale (VAS)], vascular involvement [Raynauds phenomenon (RP)], skin involvement [modified Rodnan skin score (mRss)], and ADL capacity [the scleroderma Functional Score (FS)]. Results: Hand mobility and ADL capacity were in general good and did not change significantly. However, at the individual level 72% of the patients showed a change in HAMIS score. Grip force and perceived hand function were moderately impaired at baseline and during the follow‐up. Skin involvement in the hand/arm improved significantly (p<0.001). During the observation period, the hand/arm mRss and HAMIS score changed in parallel (rs = 0.58, p<0.001). ADL capacity correlated significantly with grip force, self‐assessed hand function, and RP at baseline, and also with HAMIS at follow‐up. Conclusions: In this study hand mobility and ADL capacity were maintained during the first years of SSc. HAMIS was found to be a feasible test for longitudinal assessment of hand mobility in SSc.

Hip involvement in early rheumatoid arthritis.

OBJECTIVE--To study early hip involvement in rheumatoid arthritis (RA) and to evaluate the usefulness of ultrasonography in the detection of hip joint synovitis in RA. METHODS--Study I: The number of hip joint replacements was recorded in a cohort of 113 patients with RA of at least five years disease duration followed from an early stage. Study II: Ultrasonography was evaluated as a method to identify hip joint synovitis in 76 patients with RA of shorter disease duration, by relating it to radiograms and clinical findings. RESULTS--Study I: Twenty one hip joint replacements were performed in 15 of the 113 patients. The median disease duration at the time of first arthroplasty was 48 (range 10-76) months; the annual incidence was approximately constant between two and six years. High disease activity at the start of the study was predictive of requirement for hip prosthesis. Study II: Hip ultrasonography was pathological in 13 of the 76 patients studied, bilaterally in nine. Hip joint synovitis could not be confirmed on clinical grounds only as seven of the patients with positive ultrasonographic findings were asymptomatic, and the remaining six patients had only mild symptoms of hip involvement. Also, six of the 63 patients with normal ultrasonography had mild symptoms. There was no difference regarding demographic, clinical, and laboratory findings in patients with and without hip synovitis. CONCLUSIONS--Early hip joint destruction giving symptoms mostly at a very late stage is frequent in RA. Ultrasonography rather than signs or symptoms could identify patients with hip joint involvement and provide a rationale for early treatment.