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ID PMID Title PublicationDate abstract
10743799 Consequences of delayed therapy with second-line agents in rheumatoid arthritis: a 3 year 2000 Mar OBJECTIVE: To assess the longterm effect of delaying therapy with second-line agents in patients with early rheumatoid arthritis (RA). METHODS: One hundred nineteen patients who participated in a 9 month placebo controlled randomized trial of hydroxychloroquine sulfate (HCQ) were followed prospectively for an additional 3 years. Those randomized to HCQ are referred to as the early treatment group and those randomized to placebo as the delayed treatment group. Participants were assessed annually for pain [Arthritis Impact Measurement Scales (AIMS) and Stanford Health Assessment Questionnaire (HAQ)], physical disability (AIMS and HAQ), and the RA global well being scale (AIMS). Conversion of results into standard deviation (SD) units permitted defining a substantial difference as per Felson as > 0.30 SD units and a clinically indistinguishable difference as < or = 0.06 SD units. RESULTS: One hundred fifteen patients (97%) participated and complete data were available on 104 (87%). Compared to the early treatment group, the delayed group remained worse for both the pain and the physical disability outcomes over the additional 3 year followup. The difference in the RA global well being score became clinically indistinguishable for the early and delayed groups only after the 2 year post-trial assessment. The between-group differences were not explained by post-trial therapy with corticosteroids, other second-line agents, or nonsteroidal antiinflammatory drugs and analgesic preparations. CONCLUSION: These findings show that a delay in instituting therapy with second-line agents, even a 9 month delay in instituting a moderately powerful second-line agent such as HCQ, has significant effects on longterm patient outcome, and provides strong evidence in support of early therapy in RA.
11406046 Thermotherapy for treating rheumatoid arthritis. 2001 BACKGROUND: Heat and cold therapy are often used as adjuncts in the treatment of rheumatoid arthritis by rehabilitation specialists. OBJECTIVES: To evaluate the effects of heat and cold on objective and subjective measures of disease activity in patients with rheumatoid arthritis. SEARCH STRATEGY: We searched Medline, Embase, PEDro, Current Contents, Sports Discus and CINAHL up to June 2000. The Cochrane Field of Rehabilitation and related therapies and the Cochrane Musculoskeletal Review Group were also contacted for a search of their specialized registers. Handsearching was conducted on all retrieved articles for additional articles. SELECTION CRITERIA: Randomized or controlled clinical trials of ice or heat compared to placebo or active interventions in patients with rheumatoid arthritis and case-control and cohort studies were eligible. No language restrictions were applied. Abstracts were accepted. DATA COLLECTION AND ANALYSIS: Two independent reviewers identified potential articles from the literature search. These reviewers extracted data using pre-defined extraction forms. Consensus was reached on all data extraction. Quality was assessed by two reviewers using a 5 point scale that measured the quality of randomization, double-blinding and description of withdrawals. MAIN RESULTS: Three studies (79 subjects) met the inclusion criteria. There was no effect on objective measures of disease activity (including inflammation, pain and x-ray measured joint destruction) of either ice versus control or heat versus control. Patients reported that they preferred heat therapy to no therapy (94% prefer heat therapy to no therapy). There was no difference in patient preference for heat or ice. No harmful effects of ice or heat were reported. REVIEWER'S CONCLUSIONS: Since patients preferred thermotherapy to no therapy, thermotherapy can be used as a palliative therapy which can be applied at home as needed to relieve pain. These results are limited by the poor methodological quality of the trials.
9259433 Nitric oxide as S-nitrosoproteins in rheumatoid arthritis. 1997 Aug OBJECTIVE: Nitric oxide (NO) is a free radical involved in inflammation and immune reactions. The presence of NO is usually assessed by assaying its degradation products, nitrite and nitrate. NO binds to thiol-containing proteins to form S-nitrosoproteins (S-NP). The aim of this study was to investigate the presence of S-NP, together with nitrite and nitrate, in patients with rheumatoid arthritis (RA). METHODS: Forty patients with RA were studied and compared with 24 patients with osteoarthritis (OA) and 21 control subjects. Fourteen patients were treated with 3 consecutive pulses of methylprednisolone for flares of RA. Nitrite was measured by the Griess reaction, and nitrate by a spectrophotometric assay using nitrate reductase. Spectrofluorometry coupled with the inner filter effect was used for the measurement of S-NP. RESULTS: S-NP was detected in all RA samples, both in serum and synovial fluid (SF). Serum and articular S-NP concentrations were correlated (P < 0.03). In RA, nitrite and S-NP levels were higher in SF than in serum; higher SF levels of the 3 compounds were observed in RA than in OA. S-NP levels in RA patients decreased significantly (P < 0.03) after pulse methylprednisolone treatment, in parallel with the clinical improvement. CONCLUSION: S-NP, a biologically active form of NO, was consistently present in RA, with higher concentrations within the arthritic joint. S-NP assays should be added to nitrite and nitrate assays for the evaluation of NO metabolism. S-NP could be a stable storage form of active NO in RA, and its measurement could be useful in evaluating pharmacologic interventions that modulate NO generation.
9517757 Patterns of radiological progression in early rheumatoid arthritis: results of an 8 year p 1998 Mar OBJECTIVE: To describe the course of radiological progression in a cohort of 126 patients presenting with early nonerosive rheumatoid arthritis (RA). METHODS: Criteria for recruitment to the study were fulfillment of the 1958 American Rheumatism Association criteria, absence of erosive disease at presentation and duration of symptoms less than 3 years. Radiographs of hands and feet at 0, 1, 2, 5, and 8 years were available on 114 patients and were scored by Sharp's method for erosion (ERO) and joint space narrowing (JSN). Eighty-six patients were typed for the RA susceptibility shared HLA-DR epitope. RESULTS: The feet showed greatest initial radiological progression, but tended to reach an earlier and lower plateau. ERO progressed more rapidly than JSN in the first 2 years, but in parallel thereafter. The relative proportion of ERO:JSN varied, 1:1 for the wrists, 4:1 for the proximal interphalangeal joints. Thirty-eight percent of joints were eroded at 2 years, 63% at 8 years. Four patterns of radiological progression were identified: flat or nonerosive disease in 29 patients, linear in 51, lag in 13, and plateau in 19 (irregular in 2). Changes in the rate of radiological progression were reflected by the time-integrated C-reactive protein over the same period. Rheumatoid factor titer was higher in the progressive groups compared to the flat group (p = 0.01). The RA susceptibility shared HLA-DR epitope was more frequent in the linear compared to the flat group (p = 0.03). CONCLUSION: A large proportion of joints become eroded in the first 2 years of early RA. The subsequent course of radiological progression is highly variable and cannot be easily explained by any single model.
9615145 [Surgical treatment of the rheumatoid forefoot by realignment using th dorsal approach]. 1997 PURPOSE OF THE STUDY: The aim of this study was to appreciate the results of the modified Fowler's procedure in the surgical treatment of forefoot deformities due to rheumatoid arthritis. MATERIAL AND METHOD: If the principles of the metatarsophalangeal resection through a dorsal transverse incision were conserved, we progressively modified the initial procedure with renunciation to the plantar skin incision, preservation of a skin bridge between the medial and transverse dorsal approach, using centro medullary pins to hold in position toes alignment and making an arthrodesis of the first metatarsophalangeal joint. Ten patients (17 surgical procedures) were clinically and roentgenographically reviewed at an average follow-up of 27.3 months (Range : 12 and 53 months). RESULTS: Clinical results according to the Gainor scale showed an increase of the overall score from 3.4 points to 11.2 points at revision. Twelve foot were rated excellents and five goods. Seventy per cent of patients had no pain and 58 per cent used a normal footwear. Radiographical and clinical analysis showed that an egyptian foot remained in nine cases, podoscopic examination revealed frequently a lack of footrest on lateral toes without functional implications. Delayed wound healing were observed in four cases with good evolution. CONCLUSION: With this surgical procedure, our functional results were encouraging and we recommend it in severe deformities of the rheumatoid foot with fixed metatarsophalangeal dislocations and bone defect of the metatarsal heads.
11812023 Metalloproteases and inhibitors in arthritic diseases. 2001 Dec Controlling degradation of the extracellular matrix is crucial in arthritic diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA), as conventional treatments do not positively affect the structural properties of the articular tissues. Metalloproteases, a family of zinc-dependent enzymes, and more specifically the matrix metalloproteases (MMPs), play a premier role in joint articular tissue degeneration. Additional enzymes of the metalloprotease family, such as the membrane-type metalloproteases (MT-MMPs) and the adamalysins that include the ADAMs and the ADAMTS families, have also been found to be involved in these disease processes. At present, therapeutic intervention based on the inhibition of metalloproteases, and more particularly of the MMPs, is under intensive investigation, and several MMP inhibitors are in clinical development. Currently, MMP inhibitors are exemplified by several chemical classes: hydroxamic acids, carboxylic acids and thiols. One key issue in the clinical development of MMP inhibitors relates to whether broad-spectrum inhibitors active against a range of different enzymes or selective inhibitors targeted against a single enzyme or particular subset of the MMPs represents the optimal strategy. In this chapter, we address the different metalloprotease enzymes and sub-families and their implication in arthritic diseases. Furthermore, we assess physiological and chemical metalloprotease inhibitors, and for the latter, the current inhibitory classes of compounds being studied.
9160279 Determination of future health status expectation in rheumatoid arthritis. 1997 Apr While examining the relationship between, neuroticism, somatic factors and future health status expectation in rheumatoid arthritis (RA) patients, the present study found a considerable level of pessimism in patients, which may be related to perceived limitation of the quality of life. However, psychosocial disposition (i.e., neuroticism) did not prove to be a crucial factor by which RA patients assessed their future health status expectation. These results may be important in future treatment procedures.
10418064 Pneumococcal polyarticular septic arthritis in a patient with rheumatoid arthritis. 1999 Jun Rheumatoid arthritis is the most commonly reported host-related risk factor for septic arthritis. This risk is highest in severe, seropositive, long-standing (mean, 10 years) rheumatoid arthritis responsible for extraarticular symptoms and treated with systemic glucocorticoids. The clinical presentation of the joint infection is often atypical, leading to diagnostic wanderings. In 25% of cases, the infection is polyarticular, with 3.5 involved joints on average. Staphylococcus aureus is the most common causative organism. Streptococcus pneumoniae causes 5% of all cases of septic arthritis and is more often responsible for polyarticular infections than other organisms. Polyarticular septic arthritis carries a poor prognosis, with a mortality rate of 50% in rheumatoid arthritis patients. Despite its low incidence, polyarticular septic arthritis should be routinely considered in the differential diagnosis of rheumatoid flares. We report a case of pneumococcal septic arthritis involving five joints in a patient with known rheumatoid arthritis. Three other cases with involvement of more than four joints have been published.
9237933 B-cell activation and development within chronically inflamed synovium in rheumatoid and r 1997 Aug In autoimmune diseases, B cells often accumulate in the affected tissue. In patients with rheumatoid arthritis or reactive arthritis, germinal center-like structures may develop in the inflamed synovial tissue. B cells from these structures were isolated and their V-gene repertoire determined. The majority of synovial B cells are long-term memory cells and thus are part of the chronic inflammatory reaction. In the synovium a micro-environment is built up which allows the activation of naive and memory B cells and the diversification of their V-gene repertoire. The analysis of plasma cells suggests that these cells are long lived and hence accumulate in the synovial tissue under chronic activation.
10637965 [Adhesion molecule ICAM-1 in patients with chronic polyarthritis--effects of inpatient reh 1999 In rheumatoid arthritis (RA) the adhesion molecule ICAM-1 mediates the adhesion of leucocytes following subsequent transendothelial migration including interactions and adhesion of several cell types such as fibroblasts, T-lymphocytes and synoviocytes. Significantly increased ICAM-1 levels were measured in the acute phase of RA. The correlation of ICAM-1 levels with the pteridine neopterin (p < or = 0.01) may reflect the role of this adhesion molecule in modulation of immune responses. Despite the significantly higher levels of acute phase reactions parallel to the elevated ICAM-1 levels, no correlations were found between ICAM-1 and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and serum-Amyloid A (SAA). During an in-patient multidisciplinary rehabilitation programme the levels of ICAM-1 in serum and the majority of all investigated laboratory and clinical parameters such as ESR, CRP, SAA, fibrinogen, pain, swollen and painful joint count, morning stiffness and health assessment questionnaire improved.
9266139 Rescue of DMARD failures by means of monoclonal antibodies or biological agents. 1997 May Over the past decade different monoclonal antibodies or other biological agents have been developed to complete the available therapeutic repertoire for treating RA patients. Thus, monoclonal antibodies to block the TNF-alpha or TNF-alpha receptor fusion proteins, respectively, have been successfully applied in the treatment of RA patients refractory to other treatment principles. In addition, using the IL-1 receptor antagonist, similar promising data have been obtained in placebo-controlled, double-blind trials. Initial attempts are presently being conducted to test combination therapies, using monoclonal antibodies directed against the proinflammatory cytokines and cell surface molecules, and long-acting rheumatic drugs such as methotrexate. Hopefully within the next few years newly developed biological agents will be available for use in daily clinical practice.
11822785 Clinical and biochemical response to single infusion of clodronate in active rheumatoid ar 2001 Dec OBJECTIVE: To investigate the efficacy and tolerability of intravenous clodronate in patients with rheumatoid arthritis (RA). TREATMENT AND METHODS: Twenty-six patients with active RA were randomly allocated to receive either a single iv. infusion of placebo or 600 mg clodronate. Efficacy and safety were assessed weekly during the following three weeks by clinical and laboratory evaluations. RESULTS: Serum osteocalcin and carboxyterminal propeptide of type I procollagen (markers of bone metabolism) were significantly decreased in the clodronate group at the end of the study, whereas the indices of disease activity including number of swollen joints, number of tender joints, patient's and doctor's estimation of condition (visual analogue scale), erythrocyte sedimentation rate and serum C-reactive protein level were not affected by clodronate treatment. No serious adverse effects were observed. CONCLUSIONS: A single infusion of clodronate in patients with RA was safe and caused a decline in the markers of bone metabolism, but this short-term treatment did not suppress disease activity. Results from recent clinical and preclinical studies, however, suggest that the anti-inflammatory efficacy of clodronate requires liposome encapsulation.
10765931 Influence of polymorphism in the manganese superoxide dismutase locus on disease outcome i 2000 Apr OBJECTIVE: To determine whether polymorphism in the manganese superoxide dismutase (MnSOD) gene is associated with susceptibility or disease outcome in rheumatoid arthritis (RA). METHODS: We used a case-control approach with 153 RA patients and 218 control subjects to examine for any associations between MnSOD genotypes and susceptibility to RA. We also investigated the influence of genotypes on radiologic outcome, as measured using the Larsen score for radiographs of the hands and feet, and on functional outcome, as assessed by the Health Assessment Questionnaire. MnSOD typing was carried out using polymerase chain reaction-based methods. Results were analyzed using multiple regression analysis, with adjustment for age, sex, and disease duration. In separate analyses, we corrected for rheumatoid factor (RF) status and/or the presence of the HLA-DRB1 "shared epitope" (SE). We also examined whether radiologic outcome was influenced by interactions between MnSOD and glutathione S-transferase (GST) genes. RESULTS: No association between MnSOD genotype and development of RA was found. The MnSOD VV genotype was associated with a significantly higher (P = 0.04) Larsen score (104.4) than MnSOD AA (83.0), while MnSOD AV was associated with an intermediate score (91.8). Correction for RF status had no significant effect on the results of the analysis, but significance was lost (P = 0.09) after correction for the presence of the SE. There was evidence of interaction between the GSTT1 and MnSOD genotypes, with the MnSOD VV/GSTT1-null combination being associated with the highest Larsen score (142.1; P = 0.007 after correction for the SE). CONCLUSION: Polymorphism in the MnSOD gene is not associated with susceptibility to RA. Our data suggest that MnSOD VV is associated with more severe radiologic outcome, although this relationship may not be independent of the effect of the SE. However, interaction between MnSOD and GST genes appears to influence radiologic outcome independently of the SE.
11172281 Socket wear in bilateral simultaneous total hip arthroplasty. 2001 Jan A total of 51 patients with bilateral simultaneous Charnley total hip arthroplasties were studied for wear behavior. The mean observation time was 14.7 years. Fourteen hips had been revised during follow-up. The mean wear rate was 0.071 mm/y for left hips and 0.081 mm/y for right hips. There were considerable side differences for individual patients and little agreement between the wear measurements of left and right hips. Linear wear was increased in men, in patients with high body weight. Linear wear after hip arthroplasty is not side related.
9057794 Neurohumoral mechanisms in rheumatoid arthritis. 1997 The observation that following stroke or peripheral nerve injuries the development of rheumatoid arthritis is either prevented or ameliorated in the affected limb was the first observation of the involvement of the neurological system in the pathogenesis of the disease. Much subsequent work has established that there are intimate and intricate associations between the central nervous system, the endocrine system and immuno-inflammatory mechanisms. The predominant interaction is through the hypothalamic-pituitary adrenal axis which mediates the secretion of corticotrophin releasing hormone which then stimulates the pituitary to release ACTH. A subsequent stimulation of the adrenal cortex leads to glucocorticoid release with their known potent anti-inflammatory effects. Many factors can interact within the central nervous system to modify this pathway. Of particular relevance is the observation that the hypothalamic-pituitary adrenal axis may be defective in rheumatoid arthritis. This has implications not only in terms of pathogenesis but also in the way in which glucocorticoids are used for the treatment of rheumatoid arthritis.
9641520 Rotator cuff tear associated with an acromioclavicular cyst in rheumatoid arthritis. 1998 We report two cases of a full-thickness rotator cuff tear followed by acromioclavicular cyst formation in patients with longstanding erosive polyarticular rheumatoid arthritis. One of the consequences of a rotator cuff tear is articular instability with upward migration of the humeral head. The ensuing chronic friction against the undersurface of the acromioclavicular joint caused by arm movements can lead to a non-inflammatory effusion of the acromioclavicular joint with cyst formation. Clinical and ultrasonographic features and a pathogenetic hypothesis are discussed.
11037893 Fcgamma receptor type IIIA is associated with rheumatoid arthritis in two distinct ethnic 2000 Oct OBJECTIVE: To investigate a possible association between a functional polymorphism in the intermediate-affinity receptor for IgG called Fc-gamma receptor type IIIA (FcgammaRIIIA [CD16]) and rheumatoid arthritis (RA). METHODS: This was an allelic association study in which a single nucleotide polymorphism in FcgammaRIIIA was examined as a susceptibility and/or severity factor for RA. The FcgammaRIIIA-158V/F polymorphism was genotyped by direct sequencing in 2 well-characterized ethnic groups, UK Caucasians (141 RA patients and 124 controls) and North Indians and Pakistanis (108 RA patients and 113 controls). RESULTS: The FcgammaRIIIA-158V/F polymorphism was associated with RA in both ethnic groups (P = 0.028 for UK Caucasians, P = 0.050 for North Indians and Pakistanis, and P = 0.003 for both groups combined). FcgammaRIIIA-158VF and -158W individuals had an increased risk of developing RA in both populations (UK Caucasians odds ratio [OR] 1.6, P = 0.050; North Indians and Pakistanis OR 1.9, P = 0.023; and combined groups OR 1.7, P = 0.003). In the UK Caucasian group, the highest risk was for nodular RA, a more severe disease subset, associated with homozygosity for the FcgammaRIIIA-158V allele (OR 4.4, P = 0.004). There was also evidence for an interaction between the RA-associated HLA-DRB1 allele and the presence of at least 1 FcgammaRIIIA-158V allele in predicting susceptibility to RA (OR 5.5, P = 0.000). CONCLUSION: We have demonstrated that the FcgammaRIIIA-158V/F polymorphism is a susceptibility and/or severity marker for RA in 2 distinct ethnic groups. This finding may ultimately provide additional insights into the pathogenesis of RA and other autoantibody/immune complex-driven autoimmune diseases.
9116980 Gold-induced pulmonary disease: clinical features, outcome, and differentiation from rheum 1997 Mar Gold-induced pulmonary disease is difficult to diagnose, especially, in the case in which interstitial pneumonia appears in the course of gold therapy for rheumatoid arthritis. We analyzed the literature to define the clinical features and prognosis of gold-induced pulmonary disease, and to identify those features that distinguish gold-induced pulmonary disease from pulmonary disease secondary to the underlying disease process of rheumatoid arthritis. Relevant articles from the medical literature were identified using a Mediline search, and the bibliographies of the articles were retrieved. These works were critically reviewed for information on the clinical, physiologic, radiographic, pathologic, and bronchoalveolar lavage (BAL) findings. A total of 140 cases of gold-induced pulmonary disease were identified from 110 reports. In 81% of the patients, gold was being used to treat rheumatoid arthritis, bronchial asthma (6%), pemphigus (5%), or other processes (9%). Side effects other than pulmonary toxicity were common, and included skin rash (38%), peripheral eosinophilia (38%), liver dysfunction (15%), and proteinuria (22%). Only the presence of pemphigus or liver dysfunction correlated with a bad prognosis. Gold-induced pulmonary disease most often followed improvement in rheumatoid arthritis, presumably induced by gold therapy. BAL lymphocytosis and computed tomography (CT) scan findings are useful in making a diagnosis of gold-induced pulmonary disease in an appropriate clinical setting. Features that distinguish gold-induced pulmonary disease from rheumatoid lung disease include female predominance, presence of fever or skin rash, absence of subcutaneous nodules or finger clubbing, low titers of rheumatoid factor at onset of lung disease, lymphocytosis in bronchoalveolar lavage fluid (BALF), and alveolar opacities along the bronchovascular bundles on chest CT scan. Gold-induced lung disease is a distinct entity that can be distinguished from rheumatoid lung disease. It usually improves with cessation of therapy or treatment with corticosteriods.
9330941 The limited value of the Health Assessment Questionnaire as an outcome measure in short te 1997 Oct 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.
9059137 The timing of glucocorticoid administration in rheumatoid arthritis. 1997 Jan OBJECTIVE: To test the hypothesis that the timing of prednisolone administration might be critical in determining its effect on the diurnal rheumatoid inflammatory process. METHODS: 26 patients with rheumatoid arthritis were randomly divided into two equal groups and allocated to low doses of prednisolone at either 2.00 am or 7.30 am. Because of the diurnal variation in disease activity in rheumatoid arthritis, assessments of the two study groups were performed at 7.30 am both at the start of the study (day 1) and after four doses of prednisolone (day 5). The study protocol differences in the time period from the last dose of prednisolone to assessment were 5.5 hours in the 2.00 am group and 24 hours in the 7.30 am group. RESULTS: Administration of low doses of prednisolone (5 or 7.5 mg daily) at 2.00 am had favourable effects on the duration of morning stiffness (P < < 0.001), joint pain (P < 0.001), Lansbury index (P < < 0.001), Ritchie index (P < < 0.001), and morning serum concentrations of IL-6 (P < 0.01). The other study group showed minor but significant effects on morning stiffness (P < 0.05) and circulating concentrations of IL-6 (P < 0.05). Modest and similar improvements of C reactive protein, serum amyloid protein A, and erythrocyte sedimentation rate were seen in both study groups. CONCLUSIONS: Administration of low doses of glucocorticoids with a rather short biological half life seems to improve acute rheumatoid arthritis symptoms if it precedes the period of circadian flare in inflammatory activity, as defined by enhanced IL-6 synthesis. Further studies are needed to test the relative merits of different timing protocols of glucocorticoid administration in rheumatoid arthritis.