Showing papers in "The Journal of Rheumatology in 1995"

Inter and intraobserver variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis

Abstract: Objective. Assessment of the inter and intraobserver variability of the modified Rodnan (m-Rodnan) total skin thickness score by clinical palpation [a commonly used outcome measure in trials of systemic sclerosis (SSc)]. Methods. Skin thickness was assessed by clinical palpation of 17 body areas on a 0 to 3 scale (normal, mild, moderate, severe). The m-Rodnan total skin thickness score was derived by summation of the scores from all 17 body areas. Using the m-Rodnan, 6-7 investigators assessed skin thickness in 5-6 patients with SSc (22 patients and 23 examiners total) at each of 4 sessions for the determination of interobserver variability (accuracy). In addition 21 of the investigators then assessed m-Rodnan in 2-3 patients each (60 patients total) 3 times over a 2-8 week period to quantitate intraobserver variability (reliability). Results. Interobserver and intraobserver mean ± within patient standard deviations (SD) for the m-Rodnan were found to be 17.7 ± 4.6 and 20.7 ± 2.45, respectively. Conclusion. The m-Rodnan total skin thickness score is at least as reliable for measuring skin thickness in SSc as are the ARA and Ritchie joint tenderness counts for assessing joint disease in rheumatoid arthritis. These data are useful for the determination of sample size and for the definitions of clinically meaningful response. Assessment of skin score is sufficiently reproducible to include as a measure of disease outcome, especially if patients are serially evaluated by the same investigator. (J Rheumatol 1995 ;22 :1281-5)

Mortality studies in systemic lupus erythematosus. Results from a single center. I. Causes of death.

Abstract: Objective To study the causes of death in patients with SLE, followed prospectively in a single center. Methods The study population comprised 665 patients with systemic lupus erythematosus (SLE). Causes of death were determined by review of hospital files, autopsy reports, and death certificates. Nonparametric lifetable models were used to calculate Kaplan-Meier estimates of survival probabilities. Results One hundred and twenty-four patients (18.6%) had died. The primary causes of death were active SLE in 20 (16%), infection in 40 (32%), acute vascular event in 19 (15.4%), sudden death in 10 (8.1%), organ failure in 6 (4.8%), malignancy in 8 (6.5%), others in 8 (6.5%), and unknown in 13 (10.5%). Death as a result of active SLE was more common in patients who died within 5 years of diagnosis compared to those dying after 5 years (p = 0.021), and deaths due to vascular events and end organ failure not related to active lupus were more frequent in the late death group (p = 0.028). The overall 5, 10, 15, and 20 year survival rates were 93, 85, 79, and 68%, respectively. Patients with SLE had a 4.92 fold increased risk for death compared with the general population. Conclusion Survival rates continue to improve in SLE but causes of mortality vary at different stages.

Comparison of self-reported fatigue in rheumatoid arthritis and controls.

Abstract: Objective To compare self-reported fatigue in adults with rheumatoid arthritis (RA) with age and sex matched healthy controls without RA and to determine the relationships of fatigue to pain, sleep, functional status, depressive symptoms, and disease activity. Methods A sample of 51 patients with RA and 46 age and sex matched controls without RA completed self-administered questionnaires 3 times at 6-8 week intervals. Questionnaires included the Multidimensional Assessment of Fatigue scale, Sleep Survey, Health Assessment Questionnaire, and the Profile of Mood States. Patients had blood drawn for hematocrit (Hct) and C-reactive protein on the same day the questionnaires were completed. Results Fatigue scores were significantly higher in persons with RA compared to healthy controls. Fatigue did not change significantly in either group over time. Fatigue was strongly associated with poor sleep, functional disability, greater pain, more depressive symptoms, and lower Hct. Conclusion The importance of assessing fatigue in RA is confirmed. Effective management is needed to control clinical manifestations of RA that were found to be strongly associated with fatigue such as poor sleep, functional disability, pain, depressive symptoms, and lower Hct.

Aspects of fibromyalgia in the general population: sex, pain threshold, and fibromyalgia symptoms.

Abstract: Objective To investigate relationships between sex, pain threshold and fibromyalgia (FM) symptoms in the general population. Methods Data were obtained from a randomized populations survey of 3,006 persons in Wichita, KS and a subsample of 391 who completed a detailed interview and had an examination. Tender point counts, dolorimetry scores, clinical and psychological variables were measured. Results Dolorimetry scores were 2.04 kg/cm (1.42-2.66) lower in women than men, and women were almost 10 times more likely to have 11 tender points [OR 9.6 (2.00-46.3)] than men. Women are also more likely to have FM symptoms than men: "Pain all over," [OR 3.94 (1.34-11.38)], sleep disturbance [OR 3.06 (1.45-6.46)], fatigue [OR 4.52 (2.03-10.09)], and irritable bowel syndrome [OR 5.23 (1.83-14.96)]. Tender point counts are more correlated with FM symptoms than dolorimetry scores. Conclusion Symptoms of FM are correlated with pain threshold in the general population, but tender point counts correlate better than dolorimetry. These 2 measures of pain threshold assay different but overlapping factors. Pain threshold is lower in women; and women have more FM symptoms. Decreased pain threshold correlates with all of the symptoms of FM, even in those who do not meet criteria for the syndrome. This suggests that decreased pain threshold, as measured by the tender point counts, is an intrinsically important aspect of patient distress, regardless of the extent and kind of concomitant disease; and that much can be learned about patients by employing this examination.

How to apply Larsen score in evaluating radiographs of rheumatoid arthritis in long-term studies.

Abstract: Radiographs of rheumatoid arthritis in longterm multicenter trials vary in quality and precision, making the uniform evaluation of soft tissue swelling, osteoporosis and the size of erosions difficult. A modification of Larsen Score is presented in which only major differences in osseous and joint space changes are determined.

Patients with rheumatoid arthritis benefit from early 2nd line therapy: 5 year followup of a prospective double blind placebo controlled study.

Abstract: . Objective. To compare 2 treatment strategies in a prospective 5 year study of patients with rheumatoid arthritis (RA) : early treatment with slow acting antirheumatic drugs (SAARD) versus a wait and see attitude. Methods. One hundred thirty-seven patients with RA of < 2 years' duration entered a double blind placebo controlled study : patients in the early (E) group were treated with auranofin within one year of diagnosis of RA, and SAARD treatment in the initially placebo treated group was delayed 8 months compared with the former group. [The results after 2 years clearly favored early treatment (Borg G, Allander E, Lund B, et al : J Rheumatol 1988 ;15 :1747-54)]. Results. After a total observation period of 5 years in 75 representative patients, continued improvement in the E group was demonstrated, and differences between the 2 groups were maintained with regard to clinical variables, outcome measures, and radiographic evaluation. Conclusion. The results indicate the existence of a therapeutic window in RA within the first 2 years of the disease.

Measuring shoulder function with the Shoulder Pain and Disability Index.

Abstract: Objective To extend the validity of the Shoulder Pain and Disability Index (SPADI) by (1) making it suitable for telephone administration; (2) determining its convergent validity with other health status measures; and (3) assessing the responsiveness of the SPADI to clinical change. Methods Consecutive primary care patients with shoulder discomfort were followed for 3 months. At enrollment, a detailed shoulder specific history was obtained by a trained research assistant, and the Health Assessment Questionnaire (HAQ), the Medical Outcomes Study SF-20 (SF-20), and numeric and visual analog versions of the SPADI were completed by the patient. At 2, 4, and 12 weeks the numeric scaled SPADI was administered by telephone and patients rated globally the change in shoulder discomfort. Results One hundred and two subjects were enrolled; 96 completed at least one followup assessment and 75 completed all followup assessments. Subjects were men (98%), predominantly white (73%), with a median age of 60 years, and the majority had experienced shoulder discomfort for > 3 months (66%). At baseline the visual analog (VAS) and numeric scaled SPADI were highly concordant (intraclass correlation coefficient = 0.86), and the SPADI correlated substantially with the HAQ (r = 0.61) and the physical functioning (r = -0.50) and pain (r = -0.43) domains of the SF-20. The SPADI delta (baseline-followup) discriminated accurately between subjects who improved versus those who stayed the same or worsened [receiver operating characteristic cure, (ROC) = 0.91, likelihood ratio for improvement = 34]. Conclusion The numerically scaled SPADI is highly correlated with the original VAS version of the SPADI and other measures of health status. The SPADI is responsive to change and accurately discriminates among patients who are improved or worsened.

Comparison of a generic (SF-36) and a disease specific (WOMAC) (Western Ontario and McMaster Universities Osteoarthritis Index) instrument in the measurement of outcomes after knee replacement surgery.

Abstract: Objective. The discriminant validity of a generic, health related quality of life (HRQL) measure, the SF-36, was compared with that of a disease specific HRQL measure, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), in patients aged 67-99 years who had undergone knee replacement surgery 2 to 7 years previously. Methods. A stratified random sample of 1750 Medicare beneficiaries was surveyed and 1193 usable responses were obtained (after adjustment for ineligible, incapacitated, and deceased individuals). Discriminant validity of scale scores common to both instruments (pain, physical functioning, and overall score) were compared. Results. Examination of discriminant validity, using Spearman correlations, showed that the WOMAC discriminates better among individuals with knee problems, while the SF-36 discriminates better among individuals with varying levels of self reported general health status and comorbidities. Conclusion. These scales measure 2 distinct but important aspects of patients' health. These results support inclusion of both a generic and a disease specific HRQL measure in cross sectional studies.

Association between metabolic factors and knee osteoarthritis in women: the Chingford Study.

Abstract: Objective Several studies have shown an association with density and knee osteoarthritis (OA), however the role of other metabolic factors is unclear, with conflicting data in the literature. We studied the association between metabolic risk factors and k nee OA in women in the general population. Methods One thousand three women aged 45-64 from the Chingford population study completed risk factor questionnaires. Current blood pressure and ever hypertension were noted and fasting blood glucose, serum cholesterol, triglycerides, high density lipoprotein( HDL), and uric acid levels were measured. AP weight bearing radiographs were available in 979 women and scored using the Kellgren and Lawrence system. Grade 2+ (definite osteophytes) was used a definition of knee OA. Odds ratios (OR) and 95% confidence intervals were calculated for risk of knee OA in highest tertile versus lowest for death risk factor. All OR were adjusted for age and body mass index as potential confounders for OA. Results Radiological evidence of knee OA was found in 118 women (12%). For knee OA in either knee the variables significantly associated were raised blood glucose OR = 1.95 (1.08-3.59), and moderately raised serum cholesterol OR = 2.06 (1.06-3.98). For symptomatic women (n = 58) raised blood glucose OR = 2.77 (1.13-6.76), and use of diuretics OR = 2.27 (1.11-4.65) were significantly associated. For bilateral knee disease (n = 55) significant associations were found for ever hypertension OR = 3.02 (1.51-6.06), subjects taking diuretics OR = 2.84 (1.37-5.89), and both high and moderately raised serum cholesterol OR = 3.91 (1.07-14.25), and OR = 3.63 (1.00-13.88), respectively. In all categories of knee OA serum uric acid was nonsignificantly increased. No association was found with raised triglyceride or HDL levels or with current systolic blood pressure. Further adjustment for physical activity and social class did not affect the results. Conclusion These data suggest that hypertension, hypercholesterolemia, and blood glucose are associated with both unilateral and bilateral knee OA independent of obesity, and support the concept that OA has an important systemic and metabolic component in its etiology.

The association of body weight, body fatness and body fat distribution with osteoarthritis of the knee: data from the Baltimore Longitudinal Study of Aging.

Abstract: Objective To examine the association of body weight, body fatness, and body fat distribution with osteoarthritis (OA) of the knee. Methods Bilateral standing knee radiographs, taken between 1985 and 1991, of 465 Caucasian men and 275 Caucasian women subjects aged 40 and above in the Baltimore Longitudinal Study of Aging were read by one investigator for grade of OA using Kellgren-Lawrence scales. Measures of obesity, assessed at same visit as the last radiograph during this interval, included body mass index, percent body fat, and body fat distribution. Results Both men and women with definite knee OA had higher age adjusted mean levels of body mass index, while women only had higher age adjusted mean levels of percent body fat. Both women and men in the highest tertile of body mass index had significantly increased odds of both definite and bilateral knee OA; women in the middle and highest tertile of percent body fat had significantly increased odds of both definite and bilateral knee OA, and men in the highest tertile of waist-hip ratio had significantly increased odds of bilateral knee OA. After adjusting for body mass index, however, the association of percent body fat and waist-hip ratio with knee OA in women and men, respectively, was no longer significant. Conclusion These data further extend observations that body weight is associated with both definite and bilateral knee OA in both sexes, and support a stronger contribution of mechanical as opposed to systemic factors to explain this association.

The evolution of spondyloarthropathies in relation to gut histology. II. Histological aspects.

Abstract: Objective. To study prospectively the clinical evolution of different forms of spondyloarthropathy (SpA) in relation to the type of gut histology in ileocologoscopic biopsy specimens. Methods. Ileocolonoscopy was performed in 217 patients with SpA (149 men, 68 women). Three types of gut histology (normal gut histology and acute and chronic inflammatory gut lesions) were found. Clinical, laboratory, and radiological examinations were performed at start and 2 to 9 years later in 123 patients who were regularly monitored. For the remaining 94 patients clinical data were obtained by telephone. Results. Of the 123 patients monitored regularly, 40 (32 %) had normal gut histology, and 28 (23 %) had acute and 55 (45 %) chronic inflammatory gut lesions. Acute lesions were preferentially found in patients with non-ankylosing spondylitis SpA (non-AS-SpA). In the groups with normal gut histology and with chronic gut inflammation, patients with ankylosing spondylitis (AS) and non-AS-SpA were present in equal numbers. At review, clinical evolution was identical in the 3 histological subgroups. Eight patients developed idiopathic inflammatory bowel disease (IBD), one with initially acute gut inflammation, 7 with initially chronic gut inflammation. All had active AS at review. Fourteen patients with non-AS-SpA developed AS; 13 of them had initially presented inflammatory gut lesions. Three patients in the telephone group also developed IBD; all had active AS at review and initially presented chronic inflammatory gut lesions. Persistently high inflammatory serum variables, HLA-B27 negativity in the presence of sacroiliitis or AS, and inflammatory gut lesions at the first ileocolonoscopy indicate patients with SpA are at risk for developing IBD. Conclusion: Gut inflammation, mainly subclinical, could be demonstrated in 68% of patients with SpA. Acute gut inflammation was predominant in patients with reactive arthritis (ReA). The evolution to clinical remission was not influenced by the presence or the type of gut inflammation at start. Patients with non-AS-SpA with inflammatory gut lesions have greater risk of developing AS. One patient with Yersinia induced ReA developed AS and IBD. In total, 11 patients (66%) developed IBD, all initially presenting inflammatory gut lesions. Ten had chronic gut lesions, suggesting this type of gut inflammation is related to the inflammation of Crohn' s disease. This type of gut inflammation, the persistence of high inflammatory serum variables, and the absence of HLA-B27 in patients with AS are risk factors for developing IBD.

Mortality studies in systemic lupus erythematosus. Results from a single center. II. Predictor variables for mortality.

Abstract: Objective To analyze the factors associated with mortality in patients with systemic lupus erythematosus (SLE), followed prospectively in a single center. Methods The study included 665 patients with SLE followed over a 20-year period according to a standard protocol. Clinical laboratory information has been entered into a database. Univariate analysis was carried out to identify prognostic factors of death. The Cox proportional hazard regression model was used to estimate risk ratio of death. Results Renal damage, thrombocytopenia, lung involvement, systemic lupus erythematosus disease activity index (SLEDAI) > or = 20 at presentation, and age > or = 50 at diagnosis were predictive factors for mortality in the univariate as well as in the multivariate analyses. Hypertension and ischemic heart disease were significantly associated with death only in the univariate analysis. Conclusion Renal damage, thrombocytopenia, SLEDAI > or = 20 at presentation, lung involvement, and age > or = 50 at diagnosis are prognostic factors associated with mortality.

Classification criteria for polymyositis and dermatomyositis.

Abstract: Objective The establishment of classification criteria for polymyositis (PM) and dermatomyositis (DM). Methods Questionnaires inquiring about patients with DM, PM, systemic lupus erythematosus, progressive systemic sclerosis and noninflammatory neuromuscular diseases were distributed to the main medical institutes in Japan. Data were collected and analyzed by computer. Results Among skin lesions of DM, heliotrope rash, Gottron's sign and erythema or purpura on the extensor surfaces of the extremity joints were shown to be distinguishing criteria. In both DM and PM, proximal muscle weakness, muscle grasping and spontaneous pain, nondestructive arthritis or arthralgia, elevated CK or aldolase level, presence of systemic inflammatory signs, myogenic changes on EMG, positive and anti Jo-1 antibody and pathologic findings compatible with inflammatory myositis were distinguishing criteria items. Conclusion When a patient satisfies one of 3 skin lesion items and at least 4 other items, he or she shall be classified as having DM, sensitivity 94.1%. When a patient satisfies at least 4 items other than skin lesion items, he or she shall be classified as having PM, sensitivity 98.9%. Specificity of DM and PM is 95.2%.

Clinical manifestations of the antiphospholipid syndrome in patients with systemic lupus erythematosus associate more strongly with anti-beta 2-glycoprotein-I than with antiphospholipid antibodies.

Abstract: Objective. To investigate antibodies to phospholipid-free β 2 -glycoprotein-I (aβ 2 GP-I) in the serum of patients with systemic lupus erythematosus (SLE). Methods. We studied aβ 2 GP-I by Western blot, dot blot, and ELISA in 94 patients with SLE. Twenty-one had antiphospholipid syndrome (APS) by clinical and serological criteria, 33 had neither of these features, 18 had the clinical criteria for APS but no serum antiphospholipid antibodies (aPL), and 22 had positive aPL but no related clinical manifestations. As controls, we also studied 76 normal sera. Sera were also inhibited with cardiolipin micelles and tested for anticardiolipin antibodies (aCL) or aβ 2 GP-I activities. Results. Thirty-five of 39 patients with SLE with clinical manifestations of APS had serum aβ 2 GP-I, while only 2 of 55 patients with SLE without such clinical manifestations had them (p = 0.000000001). Sixteen patients with SLE with clinical APS but aPL negative were aβ 2 GP-I positive. All 35 patients with SLE who were aβ 2 GP-I positive had vascular manifestations, but these antibodies were present in only 4 of 55 patients with SLE without vascular manifestations (p = 0.00000001). No patient having either aPL or aβ 2 GP-I had clinical manifestations of APS, whereas all 19 patients positive for both antibodies had clinical APS. The aβ 2 GP-I positive, aPL negative patients with SLE had clinical APS more frequently (16/18) than did aβ 2 GP-I negative, aPL positive patients with SLE (2/24) (p = 0.00000001). The association of clinical manifestations of APS with aβ 2 GP-I was stronger than with aPL. Inhibition studies also indicate that aPL and aβ 2 GP-I are 2 different antigen/antibody systems. Conclusion. Our findings indicate that the so called APS associates strongly with antibodies recognizing phospholipid-free β 2 GP-I. There are patients' sera that also recognize cardiolipin and/or its cofactor β 2 GP-I, the latter perhaps by reacting with a neoepitope on this protein that appears after its interaction with cardiolipin. These would be the previously considered (β 2 GP-I dependent) aCL.

Radiographic progression on radiographs of hands and feet during the first 3 years of rheumatoid arthritis measured according to Sharp's method (van der Heijde modification)

Abstract: Objective. To determine the development rate of erosions and joint space narrowing in a cohort of patients during the first 3 years of rheumatoid arthritis (RA). Methods. All consecutive patients fulfilling the American Rheumatism Association criteria and seen within the 1st year of the disease were followed prospectively with biannual radiographs of hands and feet. One hundred and forty-seven patients were followed for 2 years and 90 patients for 3 years. Erosions and joint space narrowing were scored with a modified version of Sharp's method (van der Heijde modification). Wilcoxon's rank sum test was used to test differences between joints and between erosions and joint space narrowing. Results. On average, at 3 year followup most groups of joints showed about 8% of the maximum possible score. In most groups of joints about 20% of the joints were affected, At the start more foot joints were affected than hand joints. However, the increase in the number of affected joints and in the radiographic damage was similar in hands and feet. Consequently, the predominance of affected foot joints was still present after 3 years. The progression in the 3rd year was statistically significantly less compared to the 1st year. This was more pronounced for the number of affected joints than for radiographic damage. Conclusion. We found that 70% of the patients showed radiographic damage after 3 years and this group could already be selected after 1 year. Overall, +/- 18-20% of the joints were affected after 3 years, with relatively few abnormalities per joint (+/- 8% of the maximum possible score was reached). The rate of progression in the 1st year was significantly more than in the 2nd and 3rd years, indicating a flattening of the curve of radiographic progression.

Elevated cancer incidence in patients with dermatomyositis: a population based study.

Abstract: Objective To study the relationship of polymositis (PM) and dermatomyositis (DM) and cancer in Finland. Methods The medical records of 175 patients with PM and 71 with DM diagnosed between 1969 and 1985 were reviewed. The patients were followed until death or until December 30, 1990 through the files of Statistics Finland and the Finnish Cancer Registry. Results Thirty-four cases of cancer were found [standardized incidence ratio (SIR) 2.1, 95% confidence interval 1.4-2.9]. In the PM group the SIR was 1.0 (95% CI 0.5-1.8), and in the DM group 6.5 (95% CI 3.9-10). The relative risk of cancer among DM cases was very high (SIR 26, 12-48) in the first year after DM diagnosis. Conclusion DM is associated with cancer, but not PM. The risk is high among patients with DM older than 49. Cytotoxic drugs given to DM patients did not increase the risk of malignancies. DM and certain cancers seem to share etiological factors.

HLA-DRB1*0401/0404 genotype and rheumatoid arthritis: increased association in men, young age at onset, and disease severity.

Abstract: OBJECTIVE. To confirm the reported strong association between the HLA- DRB1*0401/0404 genotype and susceptibility to rheumatoid arthritis (RA), and to investigate the influence of sex, age at disease onset, and variables of disease severity on the strength of this association. METHODS. A case control design was adopted comparing the frequency of specific HLA-DRB1 genotypes between 201 Caucasian patients with RA and 139 controls. HLA typing was performed using a polymerase chain reaction based oligonucleotide approach with HLA-DR4 subtyping using an amplification refractory mutation system RFLP technique. RESULTS. The risk of RA in those carrying a single shared epitope (SE) allele was 4 times, and in those carrying 2 SE alleles, 8 times that in the SE negative individuals. This increase was highest in individuals carrying 2 different SE alleles, with the risk in *0401/*0404 cases being 26 times higher. This genotype was associated with a 90-fold increased risk in men and this was more than doubled when age at disease onset was below 30. In all patients with RA, this genotype was associated with a substantially increased risk of being rheumatoid factor positive and having subcutaneous nodules and/or radiological erosion. CONCLUSION. Possession of the HLA-DRB1*0401/*0404 genotype carries a substantially high risk for RA development specifically in its more severe forms. The risks are particularly increased in young men

Evaluating measurement responsiveness.

Abstract: Strategies to improve responsiveness of quantitative questionnaires and methods for evaluating responsiveness are reviewed. Current methods of evaluating responsiveness are not standardized and are themselves unevaluated. A conceptual model of assessing responsiveness is proposed.

Limitations of invasive modalities in the diagnosis of primary angiitis of the central nervous system.

Abstract: Objective Rheumatologists are often consulted to evaluate patients suspected of having primary angiitis of the central nervous system (PACNS). The diagnostic process relies heavily on interpreting the results of cerebral angiography and brain biopsy. We have assessed the operating characteristics of those invasive modalities in the diagnosis of PACNS: Methods The records of 30 consecutive patients referred for the evaluation of possible PACNS were retrospectively analyzed. Patients were evaluated on clinical grounds, and the diagnostic process was extended accordingly until a reasonable probability of a definable disease was present. All patients had cerebral angiography and/or brain biopsy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were assessed for each of the following diagnostic tests: cerebral angiography, brain biopsy, cerebrospinal fluid (CSF) examination, and magnetic resonance imaging (MRI). Results The final diagnostic outcomes were: PACNS in 7, lymphoproliferative disease in 4, infection in 4, demyelinating disease in 2, reversible vasospastic disorder in 6, and a variety of other nonvasculitic conditions in 7. Cerebral angiography had less than 30% specificity and PPV for PACNS: Brain biopsy had limited sensitivity and NPV (53% and 70%, respectively). CSF examination and MRI, although sensitive, lacked specificity. Conclusion In patients suspected of having PACNS, the results of invasive diagnostic modalities should be interpreted with caution. Accurate diagnosis should rarely rely on any single study and should only follow careful clinical, radiographic and pathologic correlation.

The natural history of juvenile chronic arthritis: a population based cohort study. II. Outcome.

Abstract: OBJECTIVE: To investigate the outcome in a population based cohort of patients with juvenile chronic arthritis (JCA) who were in the process of being transferred from pediatric to adult rheumatology care. METHODS: The cohort of patients born in 1968 through 1972, recruited from a population based epidemiological study in southwestern Sweden, were called to a followup after a median disease duration of 7.1 years. The study group consisted of 124 patients with a median age of 17.7 years. The disability and discomfort dimensions were evaluated using the Childhood Health Assessment Questionnaire (C-HAQ). The impact of the disease on social life was evaluated by patients and parents. RESULTS: The median C-HAQ disability index was 0.19 with a range from 0 to 2.75 (maximum possible score = 3). Sixty percent of the patients indicated some difficulty in daily activities. Female sex and a polyarticular disease course were risk factors for disability. The strongest determinants for disability were continuing disease activity and a positive IgM rheumatoid factor. Social impact of the disease was strongly linked to a raised C-HAQ disability index. CONCLUSION: Even in a population based study of JCA, which includes many mild cases, the majority of patients experienced some difficulty in daily activities when judged by themselves. This underlines the necessity to use the patient's own values in outcome studies, rather than the physician's. Further development of internationally accepted, standardized instruments to evaluate the handicap dimension of childhood arthritis is called for.

Clinical indicators of progression in psoriatic arthritis: multivariate relative risk model.

Abstract: Objective. To identify markers for severe disease in psoriatic arthritis (PsA). Methods. Patients with PsA followed prospectively according to a standard protocol over 14 years were included. Clinical and laboratory assessments of both active inflammation and clinical damage were performed at 6-month intervals according to a standard protocol. The information was entered into a computer database. Progression in damage was defined as transitions between damage states based on the number of damaged joints. Both univariate and multivariate models were developed to identify predictors for progression of damage. Results. The best model available, based on patient characteristics at the time of being first seen in the psoriatic arthritis clinic suggests that a high number of effusions and of past medications predicts progression in damage, whereas a low sedimentation rate «protects» from such progression. Conclusions. Evidence of significant inflammation at first visit predicts progression of damage in the future, suggesting that patients with PsA should be offered more aggressive treatment early in the course of their disease

Role of vascular endothelial growth factor in angiogenesis of rheumatoid arthritis

Abstract: Objective. To examine the localization and role of vascular endothelial growth factor (VEGF), an endothelial cell specific mitogen, in rheumatoid arthritis (RA). Methods. Immunohistochemical staining, reverse transcription polymerase chain reaction (RT-PCR) analysis and in situ hybridization for VEGF were performed on synovial tissues from 10 patients with RA, 5 patients with osteoarthritis (OA) and 3 autopsy cases. Results. In RA, the proliferative ratio of synovial lining cells and vascular endothelial cells was significantly higher than that in OA and normal synovial tissues. Immunohistochemical staining demonstrated that VEGF polypeptide was strongly expressed in subsynovial macrophages, fibroblasts surrounding microvessels, vascular smooth muscle cells, and synovial lining cells, but not in vascular endothelial cells of patients with RA. On the other hand, in patients with OA and normal cases, VEGF polypeptide was slightly expressed in synovial lining cells and fibroblasts. RT-PCR showed a positive reaction for VEGF messenger RNA in RA, OA, and normal synovial tissues. A large number of subsynovial macrophages, fibroblasts, vascular smooth muscle cells, and synovial lining cells from patients with RA expressed VEGF mRNA using in situ hybridization. Conclusion. In RA, VEGF is synthesized and released by a large number of subsynovial macrophages, fibroblasts surrounding microvessels, vascular smooth muscle cells, and synovial lining cells and may stimulate endothelial proliferation in a paracrine manner via VEGF receptors.

The evolution of spondyloarthropathies in relation to gut histology. III. Relation between gut and joint

Abstract: Objective. To study prospectively the clinical evolution of different forms of spondyloarthropathy (SpA) in relation to the evolution of gut histology in consecutive ileocolonoscopic biopsy specimens. Methods. Ileocolonoscopy was performed in 49 patients with SpA (34 men, 15 women). They also underwent clinical, laboratory, and radiological examinations. Two to 9 years later, a 2nd and sometimes a 3rd or 4th ileocolonoscopy was performed, and the other examinations were repeated. Results. At first ileocolonoscopy, 34 patients (69%) showed inflammatory gut lesions. At the 2nd ileocolonoscopy, 16 patients (32%) were in clinical remission; none were found to have inflammatory gut lesions. Of the 33 patients with persistent locomotor inflammation, 14 had persistent inflammatory gut lesions, predominantly the chronic type. Of these 14 patients, 6 had developed inflammatory bowel disease (IBD). None of the 15 patients with an initially normal gut histology had gut inflammation at 2nd examination. Of the 9 with initially acute lesions, 3 developed chronic lesions (1 Crohn's disease). Initial chronic lesions in 25 patients persisted in 9, of whom 5 had developed IBD. Seven of the 19 patients with non-SpA ankylosing spondylitis (non-AS-SpA) developed ankylosing spondylitis (AS); all had initially presented inflammatory gut lesions, which persisted at 2nd examination. In the 11 patients with more than 2 consecutive ileocolonoscopies, clinical remission was always associated with normal gut histology, and flares of the joint disease were related temporally to the reappearance of gut inflammation. Conclusion. This study demonstrates the close relationship between gut and locomotor inflammation in SpA. Clinical remission was always associated with normal gut histology, whereas active locomotor inflammation was usually associated with the presence of gut inflammation. Absence of gut inflammation in the SpA is a good prognostic indicator, since gut inflammation or IBD never develops in these patients. Evolution of non-AS-SpA to full blown AS or of uncomplicated SpA to a farm of IBD was always associated with gut inflammation at disease onset.

Arterial lesions in Behçet's disease. A study in 25 patients.

Abstract: Objective To identify the prognostic indicators of patients with Behcet's disease complicated with arterial lesions. Methods Retrospective chart analysis of 25 consecutive patients with Behcet's disease and angiographically proven arterial lesions. Results Occlusive lesions were present in 7 patients, aneurysms in 3, and both occlusive and aneurysmal lesions in 15. High dose corticosteroids were not effective in isolated occlusive lesions and probably contributed to one fatal infection. Death was related to aneurysms in 5 patients. Twenty-seven vascular surgical procedures were performed in 15 patients. Arterial lesions recurred in all patients who did not received postoperative corticosteroids. Within a 2 yr period after operation, the rate of therapy failure was lower in the group of patients treated with a postoperative combination of corticosteroids and immunosuppressive drugs, compared to the group treated with corticosteroids alone. In patients treated for lower limb arterial lesions, the rate of relapse was similar whether venous autologous or prosthetic grafts were used. Graft thrombosis occurred in 3/7 patients given anticoagulants and in 3/4 patients with no antiaggregant or anticoagulant therapy. Conclusion Aneurysms have a worse prognosis than occlusive lesions. High dose corticosteroids should not be systematically prescribed for isolated occlusive lesions. Surgery, when feasible, is indicated for aneurysms because they entail a high risk of rupture. Postoperative corticosteroids are necessary to prevent arterial relapse. A combination of corticosteroids and immunosuppressive therapy is more effective than corticosteroids alone. After bypass for lower limb arterial lesions, anticoagulation is warranted to prevent graft thrombosis.

Fibromyalgia versus rheumatoid arthritis : a longitudinal comparison of the quality of life

Abstract: Objective To evaluate and compare the quality of life of patients with fibromyalgia (FM) and rheumatoid arthritis (RA) Methods Forty-four women with FM and 41 with RA were studied There were 3 evaluations, with a 3-month interval Besides special and general clinical examinations, the following tests were applied: pain numerical scale (PNS), Health Assessment Questionnaire (HAQ), Fibromyalgia Impact Questionnaire (FIQ), Arthritis Helplessness Index (AHI), Modified Post-Sleep Inventory (PSI), and questions about sleep disorders and socioeconomic impact Results Results include the following: tender points (TP): FM = 139, RA = 29; PNS: FM = 72, RA = 68; HAQ: FM = 090, RA = 122; FIQ: FM = 472, RA = 425; AHI: FM = 327, RA = 318; sleep quality--mean duration of daily sleep: FM = 67 h, RA = 61; PSI scores: FM = 646, RA = 572 On questioning regarding economic impact, there was a decrease in family income for 65% of patients with FM and 751% for those with RA Fifty-five percent of patients with FM and 666% of those with RA received social security aid At followup evaluation, there was a statistically significant improvement in the following items for the patients with FM: TP count, HAQ, and AHI The patients with RA improved in number of TP and AHI Conclusion FM has a negative impact on quality of life, similar to RA Clinical, functional, and economic problems related to the disease were observed The alteration observed remained relatively stable during the study period, except for physical disability

Functional impairment and disability in early rheumatoid arthritis--development over 5 years.

Abstract: Objective To evaluate the development of functional impairment and disability in early rheumatoid arthritis (RA) Methods Sixty-three patients with definite RA with mean disease duration of about 1 year were followed for 5 years Joint inflammation was evaluated with an active joint count, and radiographic changes in hands and feet with the Larsen method Functional impairment of particular joint systems was assessed with a performance index, Signals of Functional Impairment Index, and disability with the Health Assessment Questionnaire (HAQ) Results During the observation time the disease activity decreased, and the radiographic changes of hands and feet increased significantly Joint replacements in 10 hips, 1 knee, and 1 shoulder were performed in 9 patients after median 43 months At study start almost half the patients had impaired hand function, mostly affecting finger flexion and pincer grip The most marked deterioration of joint function had occurred already after 2 years in metatarsophalangeal joints (55 %), elbow joints (35%), ankle joints (30%), shoulder joints (28%), and hip joints (25%) The median HAQ level at study start was 08, and the median change of HAQ over 5 years was 01 (not significant) The progression of dysfunction was not linear but followed a highly variable course over the years Patients with higher HAQ scores at study end could be correctly classified in 75% of the cases by the 3 factors, baseline HAQ score, female sex, and a low educational level Presence of a replaced joint did not contribute significantly, but patients with joint replacement tended to be more disabled Conclusion Functional outcome of RA after about 6 years of disease was fairly good Functional impairment of different joints had progressed, but most patients were still mildly disabled A subgroup of 9 patients had a worse disease course with rapidly progressing large joint destruction

Cardiovascular mortality in women with rheumatoid arthritis

Abstract: Objective To investigate the relationship of deaths from cardiovascular causes in mortality of women with rheumatoid arthritis (RA). There is increasing evidence that subjects with RA have increased mortality from cardiovascular causes, but little is known of its determinants. Methods Our study included all women subjects in Finland who died during 1989 and who were entitled to reimbursement for medication for RA under the national health insurance plan. Demographic data on the Finnish population and health insurance statistics were used for computations. Results Half of the 1186 deaths of women were due to cardiovascular causes. The distribution of specific diagnoses within this disease group did not differ appreciably from that in the female population as a whole. However, there was a 34% excess of deaths due to cardiovascular causes. The median age at death in women with RA was 2.5 years lower than that in the whole population with deaths due to cardiovascular causes. Conclusion Deaths due to cardiovascular causes constitute and important determinant in the surplus of mortality associated with RA in women.

Experimental assessment by high frequency ultrasound of articular cartilage thickness and osteoarthritic changes.

Abstract: OBJECTIVE Osteoarthritis (OA) is characterized by progressive loss of articular cartilage in the involved joint. Accurate, reproducible measurement of the thickness of the cartilage in vivo, however, is difficult. Because development of an ultrasonic imaging device for intraarticular use is feasible and would permit acquisition of information that could complement the assessment of articular cartilage made at arthroscopy, we evaluated the efficacy of high frequency ultrasound in assessing the thickness and subsurface characteristics of normal and OA cartilage. METHODS Blocks of human femoral cartilage and subchondral bone and chips of cartilage alone were examined in vitro with an experimental 25 MHz pulse-echo ultrasound scanner that portrayed cross sections of the cartilage as B-mode images. The gross and histologic appearance of the articular surface was used to identify specimens of unblemished, normal cartilage and OA cartilage. The speed of sound in cartilage, determined from measurements of cartilage thickness and sound transmission, was related to its biochemical composition. RESULTS The speed of sound in normal cartilage (1658 +/- 185 m/s, n = 27) was greater than that in OA cartilage (1581 +/- 148 m/s, n = 40, p = 0.06), but was not related to the cartilage water content or the concentration of uronic acid or hydroxyproline. Images of normal cartilage showed a smooth echo band at the tissue surface with a hypoechoic matrix; in scans of fibrillated cartilage the width of this band was proportional to the depth of fibrillation (r = 0.78). Ultrasonic and histologic measurements of OA cartilage thickness were closely correlated (r = 0.87) and the mean coefficient of variation for repeated measurements was 2%. CONCLUSION High frequency ultrasonic images obtained in vitro provide highly accurate and reproducible measurements of the thickness and subsurface characteristics of normal and OA articular cartilage.

Elevated levels of platelet derived growth factor and transforming growth factor-beta 1 in bronchoalveolar lavage fluid from patients with scleroderma.

Abstract: Objective. Systemic sclerosis (scleroderma, SSc) frequently affects the lungs, and interstitial pulmonary fibrosis is one of its major complications. The pathophysiology of SSc lung disease is poorly understood, but recent studies document an inflammatory process resembling that of idiopathic pulmonary fibrosis with increased numbers of activated alveolar macrophages and granulocytes in bronchoalveolar lavage (BAL) fluid. We determined levels of 2 potentially important mediators of fibroproliferative repair in BAL fluid from patients with SSc. Methods. Using Western blot and ELISA techniques we measured levels of platelet derived growth factor (PDGF) and transforming growth factor-beta (TGF-β) in BAL fluid from patients with SSc and healthy controls. The mitogenic effect of these cytokines on SSc lung myofibroblasts was determined by [ 3 H]thymidine incorporation. Results. SSc BAL fluid contains significantly elevated levels of PDGF-AA and PDGF-BB. Where TGF-β1 was significantly elevated in SSc lavage fluid, the amount of TGF-β2 was significantly less than that observed in normal lavage fluid. Myofibroblasts cultured from SSc lavage fluid exhibited enhanced [ 3 H]thymidine incorporation upon exposure to the growth factors present in SSc BAL fluid : PDGF and TGF-β1. SSc lung myofibroblasts pretreated with TGF-β1 exhibited an enhanced mitogenic effect upon stimulation by PDGF, due in part to the induction of the PDGF α receptor. Conclusion. Our studies support a role for PDGF and TGF-β1 in the pathogenesis of SSc lung disease.