Fetomaternal HLA differences and the onset and course of rheumatoid arthritis.
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Arthritis, Rheumatoid↗
Biomedical subjects
J M Hazes
Publications and source records attributed to J M Hazes.
Functional analysis of a human tumor necrosis factor alpha (TNF-alpha) promoter polymorphism related to joint damage in rheumatoid arthritis.
BACKGROUND: Functional heterogeneity in the tumor necrosis factor alpha (TNF-alpha) gene may be responsible for the TNF-alpha response in infectious and autoimmune diseases. Recently, the TNF-238 promoter polymorphism was observed as being associated with a more destructive disease in rheumatoid arthritis (RA). To determine the relation between TNF-238 and disease progression, the extent of joint destruction in a cohort of 101 RA patients followed for 12 years was analyzed. Furthermore, we have attempted to link this polymorphism to TNF-alpha gene transcription in monocytes and lymphocytes in vitro. PATIENTS, MATERIALS, AND METHODS: The extent of joint destruction determined on X-rays of hands and feet assessed after 0, 3, 6, and 12 years was compared with TNF-238 genotypes. Functional consequences of TNF-alpha gene polymorphisms using reporter gene constructs were analyzed in cells of the monocyte and lymphocyte lineage by means of transient transfection systems. RESULTS: The rate of joint damage in -238GA patients was lower than that in the -238GG patients, independent of HLA-DR4. Damage after 12 years was 76 +/- 30 for the -238GA versus 126 +/- 13 for the -238GG patients as determined by the van der Heijde's modification of Sharp's method. Furthermore, TNF-238A was found to be in linkage disequilibrium with an additional polymorphism at position -376. Functional assays revealed no significant differences in the level of inducible reporter gene expression between the TNF-238/-376 promoter constructs in the cell types tested. CONCLUSION: In a prospective study, we show that the TNF-238GG genotype contributes to progression of joint destruction in RA, independent of the presence of HLA-DR4. However, in vitro transfection assays indicate that TNF-238A by itself or in combination with TNF-376A is not likely to be of direct functional relevance for transcriptional activation. Therefore, these polymorphisms may serve as markers for additional polymorphisms in the TNF/LT locus or neighboring genes that may influence disease severity.
Adult↗
Efficacy of multidisciplinary team care programs in rheumatoid arthritis.
OBJECTIVE: To assess the efficacy of multidisciplinary team care programs in rheumatoid arthritis (RA). METHODS: Data were obtained by a Medline and a manual search of the literature through January 1997. Both the design and analysis aspects of controlled trials were evaluated. RESULTS: Forty-two papers reporting on 35 clinical trials of multidisciplinary team care were initially identified. Fifteen trials had a controlled design, nine of which were randomized. Patient characteristics, interventions, end point measures, and presentation of the data varied widely among the controlled studies. In 12 trials, inpatient (n = 6) or outpatient (n = 6) multidisciplinary programs were compared with regular outpatient care. Inpatient programs (average duration, 10 to 28 days) had a direct favorable effect on disease activity, lasting up to 1 year. The effect of outpatient programs (average duration, 1 to 2 years) was less marked, with greater improvement of functional status at the end of the treatment program shown in one study. In three trials, inpatient multidisciplinary programs were compared with similar outpatient programs. One study showed that inpatient care was more effective, whereas in two studies similar results were obtained in both groups. CONCLUSION: Favorable effects on disease activity were seen in most trials comparing short inpatient team care with regular outpatient care. Proof of efficacy of prolonged outpatient team care is scanty. Results of trials comparing inpatient with outpatient team care remain inconclusive.
Arthritis, Rheumatoid↗
Measurement of morning stiffness in rheumatoid arthritis clinical trials.
OBJECTIVE: Morning stiffness (MS) is a common problem for patients with rheumatoid arthritis (RA). However the clinical evaluation of the symptom has proved to be difficult. The aim of the study was to determine the responsiveness of two methods for measuring MS. METHODS: Data from an uncontrolled (n = 63) and a controlled study (n = 80) of inpatient multidisciplinary team care for RA were analyzed. MS was measured by its duration to maximum improvement and by its severity on a visual analog scale (VAS). The responsiveness of both assessment methods was computed by calculating effect sizes and t-statistics, and by receiver operating characteristic (ROC) curves with clinical improvement according to the definition of the American College of Rheumatology as an external criterion. RESULTS: With respect to the ability to detect a clinical improvement between admission and discharge in the uncontrolled study, and a difference in improvement between the treatment and the control group in the controlled study, the effect sizes and t-values of the VAS for severity of MS were consistently higher than those of the duration of MS. In contrast to the duration, the responsiveness of the VAS for MS compared favorably with the responsiveness of other endpoint measures. The ROC surface area of the VAS was higher than that of the duration. CONCLUSION: For the evaluation of MS in RA clinical trials, the assessment of MS by a severity score is more responsive than one based on duration and compares favorably with the performance of other endpoint measures.
Aged↗
The two-year follow-up of a randomized comparison of in-patient multidisciplinary team care and routine out-patient care for active rheumatoid arthritis.
The long-term effects of a period of 11 days of in-patient multidisciplinary team care were compared with routine out-patient care in 80 patients with active rheumatoid arthritis (RA). Endpoint measures included swollen and tender joint counts, the patient's assessment of pain, the patient's and the physician's assessments of disease activity, the ESR and the Health Assessment Questionnaire (HAQ). Two years after hospitalization, all 39 patients randomized to the in-patient group and 39 out of 41 patients randomized to the out-patient group were evaluable. At 2 yr, in the in-patient group the improvement according to mean changes from baseline was greater than that in the out-patient group for all endpoint measures except for the HAQ score, the differences not reaching statistical significance. Averaged over the time points 2, 52 and 104 weeks, the improvement was significantly greater in the in-patient group than in the out-patient group, except for the ESR and HAQ score. In conclusion, a short period of in-patient multidisciplinary team care has a beneficial effect on disease activity over a period of 2 yr and should be considered as a useful treatment modality in patients with active RA.
Adult↗
Tumour necrosis factor alpha gene polymorphisms in rheumatoid arthritis: association with susceptibility to, or severity of, disease?
Genetic factors associated with rheumatoid arthritis (RA) might involve variant tumour necrosis factor (TNF)-alpha genes. Therefore, polymorphisms at positions -308, -238, -376, -163 and +70 relative to the transcription initiation site were studied with respect to the susceptibility to, or severity of, RA. TNF-alpha genotypes of 283 RA patients and 116 healthy individuals were determined. Clinical data were obtained from patient files and questionnaires. The distribution of TNF-alpha alleles was similar in RA patients and healthy controls. With respect to disease severity, the TNF-alpha -238GA genotype was found to be associated with the absence of erosions [odds ratio (OR) 4.1, confidence interval 1.0-17]. In addition, this genotype was associated with a lower number of hand joints affected by erosions within the first 3 yr of disease onset compared to -238GG. The association between the -238 polymorphism and radiographic progression was independent of the presence of HLA-DR4. In line with this observation, the OR for the presence of erosions in patients with both risk factors (DR4 and -238GG) compared to patients who lack these factors was 11.1 (1.8-6.8). No associations between the TNF-alpha -308, +70 and -376 alleles and susceptibility to, or severity of, RA could be demonstrated. Our data indicate that the TNF-alpha -238GA genotype is associated with decreased radiologically detectable progression of RA.
Adenine↗
HLA-DRB1, DQA1, and DQB1 genotypes and risk of vasculitis in patients with rheumatoid arthritis.
OBJECTIVE: To investigate the association of rheumatoid vasculitis (RV) with the expression of the shared epitope, HLA-DRB1*04, DQA1, and DQB1 alleles. METHODS: A case-control study was designed to compare the frequency of the shared epitope, DRB1*04 alleles, DQA1, and DQB1 alleles of 31 patients with RV with that of 76 patients with rheumatoid arthritis (RA) without vasculitis. RV cases were discerned in subgroups according to presence or absence of minor skin vasculitis and major organ lesions. HLA-DRB1, DQA1, and DQB1 typing was performed by a polymerase chain reaction amplification and oligonucleotide hybridization. RESULTS: Overall, no associations were found between RV and the shared epitope, the DRB1*04 alleles, DQA1, or DQB1 alleles. The risk of developing RV with minor skin vasculitis (i.e., purpura or petechiae) was 10-20-fold increased in patients with DRB1*04, in particular in those homozygous for DRB1*04, and also in those with DRB1*0401. No such association was found for patients with major organ lesions. CONCLUSION: The occurrence of vasculitis in RA is not associated with the shared epitope. DQA1, or DQB1 alleles. However, the risk of minor skin vasculitis is higher in patients carrying DRB1*04.
Adult↗
The limited value of the Health Assessment Questionnaire as an outcome measure in short term exercise trials.
OBJECTIVE: To examine the value of the Health Assessment Questionnaire (HAQ) as an outcome measure in short term exercise trials. We studied the association of the objectives of exercise, namely joint mobility, muscle strength, and physical condition, with the HAQ. METHODS: Data for 100 patients with rheumatoid arthritis (RA) included in a study to examine the effect of exercise therapy were used for secondary analysis. Disease activity was determined by the disease activity score (DAS3), pain was scored on a visual analog scale (VAS), and depression was measured by the Dutch Arthritis Impact Measurement Scale. Aerobic capacity (VO2max) estimated from a submaximal ergometer test, grip strength (kPa), isokinetic muscle strength of the knee (Nm/kg), and the Escola Paulista de Medicina range of motion (EPM-ROM) score, a measure of general flexibility, were used as indicators for physical impairments. All variables were entered in a forward multiple regression analysis with the HAQ as dependent variable. RESULTS: The HAQ was significantly correlated with the DAS3 score (r = 0.53), pain (r = 0.51), depression (r = 0.40), joint mobility (r = 0.27), quadriceps strength (r = -0.35), and grip strength (r = -0.50), but not with physical condition. The DAS3 score was first entered in the multiple regression analysis model, followed by pain, quadriceps strength, and grip strength (R2 = 0.45). After 12 weeks of exercise therapy changes in the HAQ were significantly correlated with changes in pain (r = 0.41), in depression (r = 0.33), and in quadriceps strength (r = -0.25), but not with changes in joint mobility or physical condition. CONCLUSION: Physical impairments are weakly associated with the HAQ. The HAQ is not an appropriate instrument to detect changes in physical impairments due to short term exercise therapy.
Adult↗
[Diagnosis and course of early arthritis; study in a specialized clinic for early arthritis].
OBJECTIVE: To investigate the occurrence, diagnosis and course of all new inflammatory arthropathies seen in a special Early Arthritis Clinic (EAC). DESIGN: Prospective cohort study. SETTING: Academic Medical Hospital, Leiden, The Netherlands. METHODS: An Early Arthritis Clinic (EAC) was started in the outpatient clinic of rheumatology of Leiden University Hospital for diagnostic work-up according to protocol of patients with recent-onset arthritis. Inclusion criteria were: active arthritis with onset < 2 years without traumatic aetiology and no referral for a second opinion. RESULTS: In the first 18 months 276 patients were sent to the EAC, 212 met the inclusion criteria. After 2 weeks the following diagnoses were made: rheumatoid arthritis (RA) (58; 28%), psoriatic arthritis (8; 4%), reactive arthritis (11; 5%) sarcoidosis (9; 4%), crystal arthritis (30; 14%), osteoarthritis (8; 4%), other diagnosis (18; 8%). The remaining 70 patients (33%) were classified as arthritis e causa ignota (e.c.i.). After follow-up, the first diagnoses changed in 27 (12%) patients, of whom 20 patients originally had had the diagnosis of arthritis e.c.i. Persistent arthritis was found in 90% of RA and in 35% of arthritis e.c.i. Other forms of arthritis seldom showed persistent activity. CONCLUSION: In the EAC, RA, arthritis e.c.i. and crystal arthritis were seen most often. Almost all RA patients showed persistent arthritis, as against only a third of those with arthritis e.c.i. Because of the early diagnosis treatment could start early in patients with joint disease entailing irreversible joint destruction.
Arthritis↗
The mortality of rheumatoid vasculitis compared with rheumatoid arthritis.
OBJECTIVE: To determine whether the mortality of patients with rheumatoid vasculitis (RV) is increased in comparison with that of patients with rheumatoid arthritis (RA). METHODS: The mortality of all RV patients identified in 1980-1992 (n=61) was compared with that of 244 RA controls matched for the year the diagnosis was made in the RV cases. Hazard ratios (HR) of death were calculated with a multivariate survival analysis, adjusting for age, sex, comorbidity, treatment, and parameters of RA severity. RESULTS: The unadjusted risk of death (HR) in RV patients compared with RA controls was 1.65 (95% confidence interval [95% CI] 1.05-2.58). After adjustment for prognostic factors, the HR was reduced to 1.26 (95% CI 0.79-2.01), mainly due to removal of the effects of age and sex. No excess mortality was seen in RV patients with severe organ involvement when compared with RV patients without severe organ involvement, although the former patients were treated more often with cytostatic and immunosuppressive drugs. Infection was the main cause of death in the RV patients, and cardiovascular disease in the RA controls. Vasculitis was reported as the cause of death in only 1 RV patient. CONCLUSION: After allowance for general risk factors such as age and sex, there remains only a slight excess mortality in RV patients compared with RA controls.
Adult↗
A randomized clinical trial of in-patient multidisciplinary treatment versus routine out-patient care in active rheumatoid arthritis.
The aim of the present study was to compare the effects of in-patient multidisciplinary treatment with standard out-patient care in patients with active rheumatoid arthritis (RA). Eighty patients with active RA were randomized to receive 11 days of in-patient multidisciplinary treatment followed by standard out-patient care (n = 39), or to standard out-patient care only (n = 41). Patients were assessed at baseline, and after 2, 4, 12 and 52 weeks. In the in-patients, the improvement in variables of disease activity (weeks 2 and 4) and emotional status (weeks 4 and 12) was greater when compared with the out-patients (P < 0.05). The improvement in laboratory and functional measures did not differ between the groups. In the in-patient group, the percentage of patients responding to the American College of Rheumatology criteria for improvement was significantly greater at any time point during follow-up than in the out-patient group. A short period of in-patient multidisciplinary treatment for active RA has a direct beneficial effect on disease activity and emotional status with the favourable effect on disease activity remaining after 52 weeks.
Adolescent↗
Comparison of high and low intensity training in well controlled rheumatoid arthritis. Results of a randomised clinical trial.
OBJECTIVE: To investigate the benefit of intensive dynamic exercises in comparison to range of motion (ROM) and isometric exercises in rheumatoid arthritis. METHODS: 100 consecutive rheumatoid arthritis patients on stable medication were randomly assigned to (1) intensive dynamic group exercises which included full weight bearing exercises and conditioning exercises on a stationary bicycle while the heart rate was maintained at 70-85% of the age predicted maximum heart rate, (2) range of motion (ROM) exercises and isometric exercises in a group, (3) individual isometric and ROM exercises, and (4) home instructions for isometric and ROM exercises. Variables of physical condition, muscle strength, joint mobility, daily functioning (HAQ), and disease activity were assessed before and after the 12 week exercise course, and 12 weeks thereafter. An intention to treat analysis was performed. RESULTS: Increases in aerobic capacity (n = 77), muscle strength, and joint mobility in the high intensity exercise programme were respectively 17%, 17% and 16% and differed significantly from the changes in aerobic capacity, muscle strength, and joint mobility in the other exercise groups. No deterioration of disease activity was observed. Twelve weeks after discontinuation of the exercise course the gain in physical capacity had disappeared. CONCLUSIONS: Intensive dynamic training is more effective in increasing aerobic capacity, joint mobility, and muscle strength than ROM exercises and isometric training in rheumatoid arthritis patients with well controlled disease.
Adult↗
How vigorously should we exercise our rheumatoid arthritis patients?
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Arthritis, Rheumatoid↗
Diagnostic and prognostic characteristics of the enzyme linked immunosorbent rheumatoid factor assays in rheumatoid arthritis.
OBJECTIVE: To determine the diagnostic and prognostic test qualities of the enzyme linked immunosorbent assays (ELISA) for rheumatoid factor isotypes in rheumatoid arthritis (RA), and to compare them with the latex fixation test. METHODS: Rheumatoid factor tests were performed in 1988 consecutive new rheumatology outpatients within two months after their first visit to the outpatient clinic of the Department of Rheumatology of Leiden University hospital. The sensitivity, specificity, accuracy, and predictive values of the tests in discriminating RA from non-rheumatoid arthritis and erosive from non-erosive disease after two years of follow up were determined and presented as receiver operating characteristic curves and post-test probability curves. RESULTS: The sensitivity of the ELISA for IgG, IgA, and IgM rheumatoid factor for RA versus all controls at optimal cut off titres was 72%, 44%, and 69%, respectively; the specificity was 52%, 84%, and 86%. For the latex fixation test the sensitivity was 66% and the specificity 91%. The post-test probability of RA, at a clinical prevalence rate of 12%, given a positive test result in the ELISAs for IgG, IgA, and IgM rheumatoid factor and the latex fixation test, was 17%, 27%, 40%, and 49%, respectively; with negative test results the probability was 7%, 8%, 5%, and 5%, respectively. The specificity of all tests in discriminating erosive from non-erosive RA at two years was low: 41%, 44%, 47%, and 58% for the ELISAs for IgG, IgA, and IgM rheumatoid factor and the latex fixation test, respectively. CONCLUSION: The ELISAs for IgG and IgA rheumatoid factor are of no significance in diagnosing RA and in the prediction of erosive disease. The ELISA for IgM rheumatoid factor is a reasonable alternative for the latex fixation test when age and gender are taken in to consideration. The specificity of all rheumatoid factor tests in discriminating erosive from non-erosive RA is low.
Adolescent↗
Factors associated with the development of vasculitis in rheumatoid arthritis: results of a case-control study.
OBJECTIVE: To investigate those characteristics of patients with rheumatoid arthritis (RA) that are associated with the development of rheumatoid vasculitis (RV). METHODS: Demographic and clinical data of 69 patients who had been diagnosed as having RV were compared with those of 138 contemporaneous control patients with RA who were not suspected to have vasculitis. Vasculitis was confirmed histologically in 96% of the subjects with RV. RESULTS: Variables associated with the development of RV were: 1) male gender, presence of increased serum concentrations of rheumatoid factor, joint erosions, subcutaneous nodules, number of disease modifying antirheumatic drugs previously prescribed, treatment (ever) with D-penicillamine or azathioprine; 2) presence of nail fold lesions and any other extrarticular feature one year before the time of diagnosis of RV; 3) treatment with corticosteroids at the time of diagnosis of RV. CONCLUSIONS: The development of RV is associated with male gender, extra-articular features, and a severe course of RA as indicated by the presence of joint destruction and need for intensive treatment with antirheumatic drugs. The strongest association was found with the presence of increased concentrations of rheumatoid factor.
Adrenal Cortex Hormones↗
Determinants of hand function in patients with rheumatoid arthritis.
OBJECTIVE: To investigate which clinical variables contribute to the function of the hand in activities of daily living (ADL) in patients with rheumatoid arthritis (RA). METHODS: In 50 patients with RA hand function in ADL was assessed by (1) the dexterity items of the Arthritis Impact Measurement Scales (AIMS), (2) direct observation of the same items by an occupational therapist, and (3) the Jebsen hand function test. A combined hand function factor was constructed by principal component analysis of the 3 hand function measures. Further assessments included measurements of muscle strength, deformity and destruction, range of motion, and local arthritis activity. After bivariate analyses, variables that correlated significantly with the measures of hand function were entered into stepwise multiple regression analyses. RESULTS: The variables having a significant correlation with most of the hand function measures were: pinch and grip strength, patient's assessment of pain and stiffness of the hands, flexion of the thumb and fingers, range of motion of the wrist, alignment of the metacarpophalangeal (MCP) joints, swan neck and Z deformities, and the Larsen erosion score. 78% of the variance of the combined hand function factor could be explained by pinch strength, stiffness of the hands, and the presence of Z deformity and ulnar deviation. CONCLUSION: Pinch and grip strength should be carefully considered in setting goals for conservative or surgical treatment of the rheumatoid hand. In addition, reported stiffness of the hands, malalignment of the MCP joints, and flexion and deformity of the thumb were the most consistent indicators of impaired hand function.
Activities of Daily Living↗
Recruitment of patients with early rheumatoid arthritis -- the Netherlands experience.
We wished to evaluate whether early arthritis clinics (EAC) contribute to the shortening of time between the onset of complaints and the moment that adequate therapy is started in patients with arthritis. We evaluated 212 patients with arthritis referred in 1993 to an EAC. A definite diagnosis could be made in 68% of the patients 2 weeks after referral. Arthritis persisted in a large majority of patients with rheumatoid arthritis and the time between disease onset and initiation of therapy could be reduced to +/-3 months. EAC are therefore helpful in achieving early effective treatment of arthritis.
Aged↗
Assessment of shoulder function in rheumatoid arthritis.
OBJECTIVE: (1) To develop a simple outcome measure of shoulder function in rheumatoid arthritis (RA), the Shoulder Function Assessment (SFA) Scale; (2) to compare the properties of this scale with those of 2 existing measures of shoulder function, the Constant Scale and the Hospital for Special Surgery (HSS) Scale. METHODS: Fifty consecutive patients with RA participated in an inpatient multidisciplinary treatment program. The SFA Scale was constructed by selecting items considered simple to assess and relevant to shoulder function by a team consisting of a rheumatologist, an orthopedic surgeon, a physical therapist, and an occupational therapist. To examine the intra and interobserver reliability in 25 patients the SFA Scale, the Constant, and the HSS Scale were assessed twice by examiner CHME, in the other 25 patients once by examiner CHME, and once by examiner EMV. The validity of all 3 scales was determined by calculating the correlation with (1) the observed shoulder function, (2) the patient's opinion of shoulder function, and (3) shoulder joint deformity. A receiver operating characteristic curve was constructed to determine the accuracy of all scales to discriminate between differences in the shoulder function of the "best" and "worst" shoulder as reported by the patient. RESULTS: The validity and the reliability of the SFA Scale were equivalent to or better than the validity and reliability of the Constant and the HSS scale. The discriminative ability of the SFA Scale was superior to both other scales. CONCLUSION: The SFA Scale is a reliable, valid, and accurate measure of shoulder function in patients with RA that can be completed within 3 minutes.
Adult↗