Predictive value of synovial fluid analysis in estimating the efficacy of intra-articular corticosteroid injections in patients with rheumatoid arthritis.

The predictive relevance of synovial fluid analysis and some other variables for the efficacy of intra-articular corticosteroid injections in 30 patients with rheumatoid arthritis and hydropsy in a knee joint was evaluated in a prospective study. At the onset of the study, the knee joints were aspirated and 30 mg triamcinolone hexacetonide injected intra-articularly. The circumferences and the tenderness scores of the knee joints were measured at onset, after two months, and at the end of the six months' follow up. Of the variables studied, synovial fluid C4, percentage of synovial fluid polymorphonuclear leucocytes, blood haemoglobin, and serum C3 correlated significantly with the decrease in knee joint circumference after two months, whereas only the percentage of synovial fluid polymorphonuclear leucocytes correlated significantly after six months. Between the patients with and without improvement in the tenderness scores of the knee joints, only serum IgM differed at the examination after two months; this was higher in patients whose scores showed no improvement.     

Diagnostic value of synovial fluid analysis in children with reactive arthritis

We report on three children with pauciarticular arthritis in whom the clinical picture and serology were compatible with both arthritis reactive to infection with Yersinia or Salmonella and with Lyme arthritis. Results of analysis of synovial fluid by polymerase chain reaction for enterobacterial or borrelial sequences were negative. Immunofluorescence with specific antibodies revealed the presence of amorphous enterobacterial antigens in synovial fluid cells. Since this staining did not reveal enterobacterial morphology, we infected synovial fluid cells of two children with juvenile rheumatoid arthritis in vitro with Yersinia or Salmonella. After 24 h typical rods were observed, but after about 1 week amorphous antigen similar to what had been found in the three patients was seen. In cases of reactive arthritis with ambiguous results of serological testing the diagnosis may be confirmed by demonstration of enterobacterial antigens in synovial fluid.     

Neprilysin levels in plasma and synovial fluid of juvenile idiopathic arthritis patients

Objective Neprilysin (neutral endopeptidase, 3:4:24:11, CD10) (NEP) is a Zn metallopeptidase linked to controlling inflammation through the degradation of neuropeptides involved in neurogenic inflammation of chronic rheumatic diseases. The aim of our study was to evaluate circulating activity and cellular expression of NEP in the plasma of 58 children with juvenile idiopathic arthritis (JIA) and 52 controls. In 20 subjects requiring local steroid injection, NEP was measured in synovial fluid.Methods Plasma and synovial NEP were evaluated using a fluorimetric technique. Neprilysin, expressed as the antigen CD10, was determined on circulating and synovial fluid cells as mean fluorescence intensity (MFI) and as percentage of positive cells by two-color immunofluorescence.Results Circulating NEP levels were lower in JIA patients than in controls (42.0±16.6 vs 76.5±24 pmol/ml per min, P<0.001), while synovial fluid NEP values were higher than circulating levels (241.4±86.2 vs 40±15.3 pmol/ml per min, P<0.001). In monocytes, the percentage of CD10-positive circulating cells and the MFI in JIA were lower than in controls (11.6±5.2% vs 41.4±13%, P<0.001 and 18.1±7.5 vs 31.2±5.4, P<0.05, respectively). On synovial monocytes, the percentage of CD10-positive cells and the MFI were higher than on circulating monocytes (35.2±14.6% vs 9.1±2.4%, P<0.001 and 66.4±5.4 vs 22.8±14.7, P<0.001, respectively).Conclusions The downregulation of CD10 expression in monocytes and the reduction in NEP activity may be linked to the enzymes role in the control of peptides involved in the inflammation. The increased levels of NEP, MFI, and CD10-positive monocytes in synovial fluid, even though in plasma, might reflect a reactive effort to control synovial proliferation.     

Nerve growth factor in the synovial fluid of patients with chronic arthritis.

Cytokines regulate nerve growth factor (NGF) synthesis during inflammatory processes. Since cytokines are also involved in the inflammatory processes of autoimmune rheumatic diseases, we examined levels of NGF in patients with rheumatoid or other types of chronic arthritis. NGF was present in the synovial fluid and synovium of patients with chronic arthritis, but was undetectable in control fluids. We conclude that NGF might be involved in the pathogenesis of arthritis.     

Regulation of peripheral blood and synovial fluid lymphocyte apoptosis in juvenile idiopathic arthritis

OBJECTIVE: Complex regulatory mechanisms are involved in the induction of apoptosis. Their impairment may play a role in the pathogenesis of several autoimmune diseases. Recently, we have described higher incidences of spontaneous apoptosis of peripheral blood (PB) lymphocytes in children with juvenile idiopathic arthritis (JIA). This study aimed to evaluate the regulatory mechanisms that may be responsible for this phenomenon. METHODS: Thirty-four JIA children were examined and compared with 20 healthy children of similar ages. Expression of regulatory proteins p53, Bax and Bcl-2 in lymphocytes isolated from PB and synovial fluid (SF) was assessed. Serum and SF levels of interleukin-15 (IL-15) were also evaluated. RESULTS: The study showed significantly decreased Bcl-2 expression in JIA PB lymphocytes, compared to both healthy control (p = 0.03) and JIA SF lymphocytes (p = 0.005). There were no significant differences found in Bax expression between groups or compartments examined. However, the Bax/Bcl-2 ratio was nearly two-fold higher in PB lymphocytes than in SF of JIA patients (p = 0.001). p53 expression in PB lymphocytes from both JIA and control children did not statistically differ. In JIA, however, p53 was significantly higher in PB than SF lymphocytes (p = 0.016). IL-15 levels were about 20-fold higher in JIA SF than in serum from either JIA or healthy children (p < 0.0001). CONCLUSION: The results suggest that a higher incidence of apoptosis of PB lymphocytes observed in JIA may be associated with down-regulation of Bcl-2, rather than with changes in expression of Bax and p53. In contrast, the low p53 expression and elevated IL-15 appear to provide mechanisms responsible for suppression of apoptosis in SF cells from JIA patients.     

Complement activation in synovial fluid and tissue from patients with juvenile rheumatoid arthritis

Synovial fluid (SF) and synovial tissue from 10 patients with juvenile rheumatoid arthritis were examined. The SFs were heterogeneous with respect to the degree of complement activation. Quantification of C3dg and the terminal complement complex revealed a positive correlation between activation of the early and the late parts of the cascade in all patients. The amount of C-reactive protein and the number of white blood cells in the SF correlated significantly with the degree of complement activation. Weak deposits of C3, C3dg, or terminal complement complex were observed in a few vessels in the synovial tissue from 5 of the patients. There was no correlation between complement activity in SF and in the corresponding tissue. Furthermore, there was no correlation between clinical activity in the joints and the degree of complement activation. It is concluded that there is a discrepancy between synovial tissue and synovial fluid with respect to complement activation. C-reactive protein may, to some extent, be responsible for activation in SF, and the accumulation of white blood cells may be due to complement activation products.     

Immunocytology of synovial fluid cells may be of diagnostic and prognostic value in arthritis.

Cells of the synovial fluid (SF) have been examined by immunocytochemical methods. Samples were aspirated from four groups of patients with knee effusions: (a) seropositive inflammatory arthritis (n = 9); (b) seronegative inflammatory arthritis (n = 9); (c) osteoarthritic patients (n = 5); and (d) patients with traumatised knees (n = 4). The proportions of lymphocyte and macrophage subsets within the SF were determined with a panel of monoclonal antibodies. Patients with inflammatory arthritis had significantly larger proportions of activated T cells (RFT2+) and macrophages with the phenotype of interdigitating cells (RFD1+). No significant difference between groups could be found on differential count or when T4+/T8+ subset ratios were calculated. No significant difference in proportions of lymphocyte or macrophage subsets was found between the groups with seropositive and seronegative inflammatory arthritis. In two of three patients, where immunocytochemical analysis was performed before and after intra-articular steroids, reductions in the proportions of RFT2+ T cells and RFD1+ macrophage like cells were seen. It is suggested that such analysis may be of diagnostic or prognostic value.     

Routine analysis of synovial fluid cells is of value in the differential diagnosis of arthritis in children

Results of synovianalysis are reported in 129 children, 91 with juvenile rheumatoid arthritis (JRA), 13 with septic arthritis, 12 with enteroarthritis, 12 with acute transient arthritis and 1 with bacillus Calmette-Guerin arthritis. Mononuclear cells were dominant in the patients with oligoarticular JRA (mean 64%, median 74%), and among these, significantly lower proportions of polymorphonuclear (PMN) cells were found in patients with early onset disease with antinuclear antibodies or chronic uveitis than in those with late onset with HLA-B27. PMN cells were dominant in polyarticular and systemic onset JRA, septic arthritis and enteroarthritis. The sensitivity and specificity of a white cell count above 40,000/mm3 exceeded 90% in differentiating septic arthritis from the other kinds of arthritis. Measurement of total protein, glucose and lactate in synovial fluid was of limited diagnostic value.     

A case of lymphoproliferative disease presenting as juvenile rheumatoid arthritis. Diagnosis by synovial fluid examination

Lymphoproliferative disease can present as arthritis, most commonly mimicking acute rheumatic fever. The finding of arthritis rarely leads to the correct diagnosis, in fact, it frequently suggests inflammatory rheumatic diseases. We present a case closely resembling juvenile rheumatoid arthritis in which the diagnosis was made by demonstration of malignant cells In the synovial fluid at a time they were absent from the peripheral blood and initial bone marrow specimen. Closed synovial and bone biopsy specimens, the latter of an osteopenic area, revealed the infiltrative character of this disorder.     

Nerve growth factor in the synovial fluid of patients with chronic arthritis

Cytokines regulate nerve growth factor (NGF) synthesis during inflammatory processes. Since cytokines are also involved in the inflammatory processes of autoimmune rheumatic diseases, we examined levels of NGF in patients with rheumatoid or other types of chronic arthritis. NGF was present in the synovial fluid and synovium of patients with chronic arthritis, but was undetectable in control fluids. We conclude that NGF might be involved in the pathogenesis of arthritis.     

Retrocalcaneal bursitis in juvenile chronic arthritis.

Retrocalcaneal bursitis has been described in various adult rheumatic diseases and septic bursitis unrelated to previous bursal disease has been reported in children. The case is reported here of a girl with juvenile chronic arthritis who developed non-septic retrocalcaneal bursitis; the diagnosis was suggested by a combination of clinical and radiographic studies and was confirmed by ultrasonography.     

Autoantibody profile in juvenile chronic arthritis.

Patients with juvenile chronic arthritis (JCA) may be subdivided into a minority, who carry IgM rheumatoid factor and have erosive polyarthritis resembling adult rheumatoid arthritis, and the majority (90%), who are seronegative by conventional means. Between 30 and 60% of patients with JCA have positive antinuclear antibodies (ANAs) according to the choice of substrate for indirect immunofluorescence. The importance of ANAs is the frequent development of associated asymptomatic chronic iridocyclitis, which may impair vision causing worse handicap than the arthritis, which remains predominantly pauciarticular in two thirds of these young children. ANA positive patients rarely possess antibodies to deoxyribonucleic acid (DNA) or extractable nuclear antigens (ENA), and current studies suggest that several different nuclear antigens, including histones, may be involved.     

Neutrophil chemotaxis in juvenile chronic arthritis.

The leucocyte infiltration observed in histological lesions from patients with juvenile chronic arthritis (JCA) suggests the possibility of an abnormal leucochemotaxis. A group of 21 patients with JCA which fulfilled the Eular criteria (Oslo Symposium 77) were investigated with a paired group of 21 children. The chemotactic assay used was a microscopical direct observation technique. The chemotaxis of the patient's leucocytes was in the normal range, as was the chemotactic activity of their serum. However, their serum had an enhancing effect on the chemotaxis of normal leucocytes. An attempt to characterise this chemotactic enhancing factor was undertaken. It was not dialysable, heat stable, destroyed at 80 degrees C, nor precipitated by ammonium sulphate at 45%; it could be migrated on PAGE with albumin, and, by precipitation with a goat antihuman albumin antiserum, seemed to be bound to the albumin fraction. The function of this factor in the regulation of the inflammatory process is discussed.