Dosing of intra-articular triamcinolone hexacetonide for knee synovitis in chronic polyarthritis: a randomized controlled study.

Objective: Intra-articular glucocorticoid (IAGC) injection treatment is an easy and effective way to treat the signs and symptoms of arthritis, but there is limited knowledge on the adequate dosing for different joints. The aim of this study was to compare the outcome between two common doses of intra-articular triamcinolone hexacetonide (THA) for knee synovitis using the relapse rate during 6 months. Methods: A total of 159 adult patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) and active knee synovitis were randomized to IAGC injection with 20 mg or 40 mg THA. Participants were blinded to the treatment dose. The primary endpoint was relapse of arthritis. When symptoms from the treated joint recurred and signs of arthritis could be confirmed on a subsequent clinical examination, a relapse was recorded and the duration of response survival was calculated. At the end of the observation period, patients without relapse were telephoned to verify the persistence of the good treatment response. Results: The proportion of relapse after 6 months was equal in the 20 mg and 40 mg THA treatment arms (30% vs 32%, respectively, p = 0.822), and no significant differences were found in the subgroups with RA and PsA patients. Conclusion: As no difference in outcome was found between the compared doses, the lower 20 mg THA dose should be preferred in IAGC treatment for knee synovitis in chronic polyarthritis. This may also reduce pharmaceutical costs and metabolic side effects. EudraCT number: 2014-000993-20, Clinical Trials.gov identifier: NCT02437461.

Pentraxin 3 in serum and synovial fluid of patients with rheumatoid arthritis with and without autoantibodies.

OBJECTIVES: Pentraxin 3 (PTX3) is a locally produced multifunctional protein involved in inflammation, matrix deposition, and immunity. As patients with seropositive rheumatoid arthritis (RA) have a more severe disease course and higher risk of joint destruction than seronegative patients, the aim of the present study was to examine differences in PTX3 in synovial fluid (SF) (and serum) in seropositive compared to seronegative RA, and other local markers of inflammation and destruction. METHOD: Ninety-seven RA patients with knee effusion were included. Serum and SF levels of PTX3, as well as serum levels of anti-citrullinated protein antibody and rheumatoid factor of immunoglobulin A and M subclasses, and markers of inflammation and potential destruction in SF: white blood cell counts, tumour necrosis factor, interleukin-6, vascular endothelial growth factor, metalloproteinase 3, and cartilage oligomeric matrix protein, were analysed. In addition, a radiographic knee examination was performed. RESULTS: Seropositive patients had significantly higher PTX3 levels in SF than seronegative patients, whereas there was no difference for serum levels. SF-PTX3 levels correlated with disease activity and with local inflammatory markers, especially polymorphonuclear cells, and with autoantibody levels. There was no correlation between PTX3 levels in serum and SF. CONCLUSION: The correlation of disease activity and autoantibody levels with SF-PTX3 levels in antibody-positive patients suggests a role for PTX3 in the inflammatory process specifically in seropositive RA joints, and supports the hypothesis that seropositive and seronegative RA are different disease entities. Polymorphonuclear granulocytes may be an important source of PTX3 in RA SF.

Serum levels of sex steroid hormones and matrix metalloproteinases after intra-articular glucocorticoid treatment in female patients with rheumatoid arthritis.

OBJECTIVES: To study metalloproteinase activity and sex steroid hormone production in serum after intra-articular glucocorticoid treatment for knee synovitis. METHODS: 18 female patients with rheumatoid arthritis and synovitis of the knee with need for intra-articular glucocorticoid treatment were included in this study. Serum samples of matrix metalloproteinases (MMP-1/TIMP complex and MMP-3), dehydroepiandrosterone sulphate, testosterone, oestradiol, steroid hormone binding globulin, follicle stimulating hormone and luteinising hormone were collected before injection with 20 mg triamcinolone hexacetonide, and 24 h, 48 h, 1 week and 2 weeks after injection, respectively. RESULTS: Serum levels of MMP-3 were significantly decreased, but MMP-1/TIMP complex was unaffected. Dehydroepiandrosterone sulphate, testosterone and oestradiol levels all decreased and tended to return to baseline levels during the observation period. Steroid hormone binding globulin, follicle stimulating hormone and luteinising hormone levels were unchanged. CONCLUSIONS: Intra-articular glucocorticoid treatment causes a temporary, but considerable suppression of sex steroid hormone secretion. The reduction of MMP-3 indicates an inhibition of the inflammatory, but probably also the cartilage destructive processes within the treated joint.

Glucocorticoid resorption and influence on the hypothalamic-pituitary-adrenal axis after intra-articular treatment of the knee in resting and mobile patients.

BACKGROUND: Studies have shown that intra-articular glucocorticoid injection treatment for knee synovitis has a better outcome in resting patients than in mobile patients. One reason for this observation might be that rest retards steroid resorption, causing an enhanced local treatment effect. OBJECTIVES: To study drug resorption and the impact on hormone production in the hypothalamic-pituitary-adrenal axis after intra-articular glucocorticoid administration, with and without postinjection rest. METHODS: Twenty patients with rheumatoid arthritis and knee synovitis were randomised to either 24 hour bed rest or normal activity after intra-articular glucocorticoid treatment with 20 mg triamcinolone hexacetonide (THA). Serum levels of THA, cortisol, and adrenocorticotropic hormone (ACTH) were followed during 2 weeks. RESULTS: Short term and reversible decreases in serum cortisol and ACTH levels (p<0.001) were seen, without any significant differences between resting and mobile patients. The THA levels increased similarly in both groups, with the median serum peak seen after 8 hours. CONCLUSION: Immobilisation does not appear to retard glucocorticoid resorption after intra-articular administration. Further studies are therefore needed to clarify the mechanism behind the beneficial effects of rest after intra-articular glucocorticoid treatment for knee synovitis.

Changes of cartilage and bone markers after intra-articular glucocorticoid treatment with and without postinjection rest in patients with rheumatoid arthritis.

BACKGROUND: Joint immobilisation improves the therapeutic effect of intra-articular glucocorticoid injection for knee synovitis. This may be due to retarded steroid resorption by immobilisation, a procedure that also could influence cartilage and bone metabolism. OBJECTIVE: To evaluate changes in cartilage and bone turnover after intra-articular glucocorticoid treatment for knee synovitis with and without postinjection rest. METHODS: 20 patients with rheumatoid arthritis and knee synovitis were randomised to 24 hour bed rest or to normal activity after intra-articular glucocorticoid treatment. Serum and urine markers of cartilage and bone turnover were studied for two weeks. Cartilage oligomeric matrix protein (COMP) was used as a marker of cartilage turnover, osteocalcin as marker of bone formation, and deoxipyridinoline (DPD) as marker of bone resorption. RESULTS: After the glucocorticoid injection COMP levels decreased in both groups (p<0.001), but significantly more in resting patients. Serum osteocalcin levels decreased significantly (p<0.001) without any difference between the groups. DPD was unchanged in both groups. CONCLUSIONS: Intra-articular glucocorticoid treatment for knee synovitis reduced serum COMP, which suggests that such treatment may have a cartilage protective effect. The slightly larger decrease of serum COMP in the resting group may reflect a lower clearance of COMP from the joint cavity. Serum osteocalcin was temporarily reduced, indicating a reversible suppression of bone formation.

Randomised controlled study of postinjection immobilisation after intra-articular glucocorticoid treatment for wrist synovitis.

BACKGROUND: Intra-articular glucocorticoid treatment is frequently used in arthritic disorders. Postinjection rest has been shown to improve the outcome of knee injections. OBJECTIVE: To investigate whether better treatment results might also be achieved by a similar postinjection regimen for the wrist, which is non-weightbearing. METHODS: 117 patients with rheumatoid arthritis and wrist synovitis were treated with intra-articular glucocorticoid injections. The patients were randomly allocated to 48 hour postinjection immobilisation in elastic wrist orthoses (n=58) or to normal postinjection activity (n=59). The primary end point was relapse of synovitis. In addition, joint circumference, pain, function, range of movement, and grip strength were followed up during six months. RESULTS: 24 relapses occurred in the orthoses group and 14 in the active group (p=0.056). The secondary measure showed no statistically significant differences between the groups. CONCLUSION: The use of elastic wrist orthoses as a postinjection regimen does not improve the outcome of intra-articular glucocorticoid treatment for wrist synovitis. Results achieved in studies on knees should not be generalised to other joints, and postinjection recommendations should differ depending on the joint treated.

Endocrine effects of the podophyllotoxine derivative drug CPH 82 (Reumacon) in patients with rheumatoid arthritis.

CPH 82 is a non-steroid antirheumatic drug containing two benzylidenated podophyllotoxin glucosides with no affinity for the glucocorticoid receptor. Treatment with CPH 82 as single drug therapy significantly decreased serum and urinary cortisol and cortisol metabolites, serum adrenal androgens and urinary androgen metabolites, plasma ACTH and serum interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), and increased serum levels of sex hormone-binding globulin (SHBG). Significant positive correlations were found between serum TNF-alpha and plasma ACTH and between serum IL-6 and TNF-alpha on the one hand and serum and urinary cortisol and cortisol metabolites on the other. The initial action of CPH 82 on adrenal steroidogenesis may be a reduction in cytokine levels due to the drugs' antiinflammatory effect. This causes decreased ACTH stimulation, resulting in a reduced adrenocortical steroid secretion. Accumulation of the drug in the adrenal cortex may also affect adrenal steroidogenesis. The elevated SHBG levels may be caused by a weak estrogenic activity of the drug.

Importance of synovial fluid aspiration when injecting intra-articular corticosteroids.

OBJECTIVE: The aim of this prospective study was to find if a complete synovial fluid aspiration before injecting intra-articular corticosteroids influences the treatment result. METHODS: The study was performed in 147 patients with rheumatoid arthritis (RA). One hundred and ninety one knees with synovitis were randomised to arthrocentesis (n=95) or no arthrocentesis (n = 96) before 20 mg triamcinolone hexacetonide was injected. The duration of effect was followed up for a period of six months. All patients were instructed to contact the rheumatology department if signs and symptoms from the treated knee recurred. If arthritis could be confirmed by a clinical examination a relapse was noted. RESULTS: There was a significant reduction of relapse in the arthrocentesis group (p = 0.001). CONCLUSION: The study shows that aspiration of synovial fluid can reduce the risk for arthritis relapse when treating RA patients with intra-articular corticosteroids. It is concluded that arthrocentesis shall be included in the intra-articular corticosteroid injection procedure.

Bacterial arthritis in a Swedish health district.

The aim of this retrospective investigation was to study the occurrence, characteristics and outcome of culture-positive bacterial arthritis in a Swedish county hospital for the period 1994-97. Using registers of diagnosis, 15 adult patients with infectious arthritis in native joints were identified. Staphylococcus aureus was, as expected, the most common microbial agent. Six cases were caused by direct inoculation. The risk for bacterial arthritis caused by intra-articular steroid injection was estimated at 1/12,000. Joint damage was seen in 6 cases. Two patients died during the infection. White blood cell count in synovial fluid was performed in 5 cases, with median value 1.9 x 10(9)/l and, since it was not a good predictor of infection in this study, the value of this method for this indication is questioned.

Occurrence of polymyositis in the county of Gävleborg, Sweden.

Through register research 21 new cases (10 male, 11 female) of polymyositis/dermatomyositis during the period 1984-1993 in the county of Gävleborg, Sweden, were identified. The case records were studied retrospectively. Inclusion body myositis was found in three cases and overlap syndrome in seven cases. Three patients had associated malignant disease. The annual incidence was estimated to 7.6 cases/million people. The clinical features are described. 19 patients were given steroid treatment, and azathioprin was the most used additive immunosuppressive drug. All patients could be followed for at least two years, and during this period three patients died (all of cancer disease). Remission and withdrawal of medication were achieved in five cases. The results of the study corresponds to previous investigations with similar design.

Serum concentrations of hyaluronan and proteoglycan in joint disease. Lack of association.

Circulating hyaluronan originating from the synovial membrane and circulating proteoglycan released from cartilage were determined by specific assays in patients with osteoarthritis (OA), rheumatoid arthritis (RA), reactive arthritis or juvenile chronic arthritis (JCA). Elevated hyaluronan concentrations were found in OA and RA, suggesting proliferation of the synovial membrane in both diseases. The proteoglycan concentrations were highest in OA and polyarticular JCA indicating increased turnover of cartilage matrix. The concentrations of the macromolecules did not correlate except in the group with JCA. Serum concentrations of hyaluronan and proteoglycan thus differ between disease groups and may reflect different aspects of the arthritic process.

Proresid in the long-term treatment of rheumatoid arthritis.

Drug withdrawal rate and reasons for treatment termination were studied in a retrospective life-table analysis of patients with rheumatoid arthritis prescribed Proresid, a semisynthetic podophyllotoxin derivative. Two years after starting with Proresid medication, half of the patients were still on treatment. After 5 years the termination rate had risen to 71%. Gastrointestinal side effects were the most common reason for abandoning medication. The results are compared with those found in other studies of similar desing. It is concluded that Proresid is a valuable and well-tolerated disease-modifying drug for long-term treatment of rheumatoid Arthritis.