Inhibition of neutrophil chemotaxis in methotrexate-treated rheumatoid arthritis patients

Summary Polymorphonuclear cell (PMN) chemotaxis was assessed using the in vitro under agarose assay in ten rheumatoid arthritis patients prior to and following a single 10-mg dose of methotrexate (MTX). PMNs obtained from patients after MTX showed a decreased chemotactic migration response to both zymosan activated serum (P<0.005) and N-formyl-L-methionyl-L-phenylalanine (P<0.01). In similar conditions, no significant difference in chemotactic migration could be detected in six rheumatoid arthritis patients not on MTX. In contrast to the in vivo effects of MTX, there was no inhibition of normal PMN chemotactic migration following a 30-min in vitro incubation of the cells with MTX (P<0.99).     

Effects of tenoxicam on neutrophil chemotaxis in rheumatoid arthritis and healthy controls

Summary Using a modified Boyden chambers method, polymorphonuclear leucocyte (pmnl) random migration and chemotactic responsiveness were compared in 20 rheumatoid arthritis patients with that of 10 healthy controls receiving tenoxicam. Random migration and chemotaxis of neutrophils were examined before drug administration, following 2 hours and 7 days of drug administration and one week after the end of the 7-day-administration of this compound. There was no statistically significant difference between the chemotactic migration of neutrophils in healthy volunteers and patients with RA. The mean chemotactic value in patients with RA and healthy controls was significantly low at 2 hours after drug administration when compared with that before drug administration (p<0.01). The comparison of the decreases in mean chemotactic values in patients with RA and healthy controls showed no statistical difference. At the end of 7-day-administration, neutrophil chemotaxis was significantly decreased in patients with RA (p<0.01); however, in healthy controls it was decreased as well, but statistical difference could not be obtained. One week after drug withdrawal, neutrophil chemotaxis turned to baseline values in both groups. We suggest that tenoxicam is a potent inhibitor of neutrophil chemotaxis.     

Juvenile rheumatoid arthritis

A satisfactory classification of arthritis in childhood has still to be defined, and a system that can facilitate communication among physicians has been proposed by an international committee. The immunopathogenesis of the diseases that are encompassed by the term juvenile rheumatoid arthritis is complex, and many studies have investigated the role of genetic and cytokine balance abnormalities. HLA associations have been confirmed in multiple series, and there is evidence that non-major histocompatibility complex genes might also contribute to disease pathogenesis. Recent studies have added knowledge to the diverse clinical features of the disease, including joint distribution at presentation, association with Turner syndrome, presence of arthritis mutilans, and alterations in mandibulofacial development. Medical treatment remains a challenge. For cases recalcitrant to conventional therapy autologous hemopoietic stem-cell transplantation has been attempted; the risks of this procedure must however be carefully balanced in individual patients.     

Juvenile rheumatoid arthritis

Progress in achieving international consensus concerning the classification of juvenile idiopathic arthritis has been made, although further refinement and validation of these criteria is needed. It is hoped that this will facilitate more effective international collaboration in the study of these diseases, because much remains to be learned about genetic susceptibility, causation, pathogenesis, and treatment. Attention to the unique aspects of chronic arthritis in children such as impaired growth and macrophage activation syndrome may help to reduce disease-related morbidity and mortality. New biologic agents have substantially enhanced the treatment of JRA. The identification of reliable predictors of disease course and outcome is important in the rational and timely application of new therapies.     

Juvenile rheumatoid arthritis.

The heterogeneous nature of juvenile rheumatoid arthritis is further defined in publications from the past year. Decreased IL-10 production, an anti-inflammatory cytokine, and soluble IL-6 receptor are associated with systemic juvenile rheumatoid arthritis (JRA). IL-4 may have an anti-inflammatory role in the pathogenesis of pauciarticular JRA and may protect, along with IL-10, against the development of joint erosions. Active JRA is associated with lower levels of platelet activating factor acetylhydrolase, which may contribute to the loss of anti-inflammatory activity and increased risk of atherogenesis. The phase 3 clinical trial of etanercept confirmed its efficacy and safety in JRA. Intra-articular steroids are safe and effective in the treatment of JRA. Methotrexate does have disease-modifying effects. The risk of hepatotoxicity with methotrexate use increases with serial transaminase abnormalities and with obesity. Osteoclasts are responsible for joint erosions. Cyclosporine A, mycophenolate mofetil, and methotrexate are effective in the treatment of refractory uveitis. During the past year a number of scientific publications have contributed significantly to our understanding and treatment of juvenile rheumatoid arthritis.     

Joint fluid leukocytosis of patients with rheumatoid arthritis evidence for neutrophil and monocyte chemotaxis in vivo

Summary The cell picture of the synovial fluid of fourteen patients with rheumatoid arthritis was studied in smears contrasted with the May-Grünwald-Giemsa stain. The cytology was dominated by neutrophils, many with signs of necrobiosis. The mononuclear cells displayed signs of proliferation and differentiation. Comparison with the immobile erythrocyte provided evidence that the accumulation of leukocytes in the synovial fluid of patients with rheumatoid arthritis was due to active leukocyte migration, presumably stimulated random movement and chemotaxis.     

Juvenile rheumatoid arthritis in Turner's syndrome

An increased risk for autoimmune diseases has been recognized in Turner's syndrome (T.S.). However autoimmune rheumatic or connective tissue disorders have not been described. We report here on a 8-8/12 year old caucasian girl with T.S. and Juvenile Rheumatoid Arthritis (JRA). The hypothesis that the association is more than casual is discussed.     

Juvenile rheumatoid arthritis in affected sibpairs

Objective. To describe the demographics and clinical disease in affected sibpairs (ASPs) with juvenile rheumatoid arthritis (JRA), and to compare JRA as it occurs in ASPs with that from non-ASP JRA populations described in the literature. Methods. A rare disease research registry was established with a focus on JRA ASPs to facilitate accrual of patients for genetic, epidemiologic, and clinical studies. Physicians likely to care for patients with JRA were made aware of the registry and its goals by a variety of methods and asked to refer patients for entry. Results. To date, 71 ASPs have been registered and complete information has been obtained. These affected sibs differed in age by a mean of 4.1 years (SD 3.4) and in age at disease onset by 2.8 years (SD 3.0). The actual time difference between onset in sib 1 versus sib 2 averaged 4.4 years (SD 4.2). Sixty-three percent of the sibpairs were concordant for sex, and 76% for JRA.Onset type within sibpairs did not appear to be random, based upon comparisons with non-ASP populations. Greater than expected concordance was seen among those with pauciarticular-onset and polyarticular-onset JRA. Seventy-nine percent of the pairs were concordant for course type. Seven sets of twins were included (∼10% of the total), all were concordant for onset and course type (6 sets with pauciarticular, 1 set with polyarticular), and disease onset was separated by a mean of only 3.3 months. Within the onset and course types, the clinical disease, such as the female:male ratio, age at onset, and serologic findings, in ASPs resembled that which has been described in the literature. Conclusion. A higher than expected degree of concordance for onset type of JRA exists between sibpairs, indicating that genetic influences play a role. Affected sibs do not tend to develop their disease at approximately the same point in time, except for the twin sets. Clinical features of the disease within the various subtypes appear similar to those in non-ASP populations.     

Impaired polymorphonuclear leucocyte chemotaxis in rheumatoid arthritis.

This study has investigated the chemotactic activity of polymorphonuclear cells (PMNs) isolated from the blood of patients with either articular rheumatoid arthritis (RA) or RA with extra-articular manifestations. A double fluorochrome immunofluorescent staining test has been employed to identify cell-associated immunoglobulins, probably immune complexes. The results suggest an inverse relationship between PMN chemotaxis and staining for cell-associated immunoglobulins, either surface bound or internalised. PMNs from RA patients showed reduced chemotaxis, and this was further reduced when RA PMNs were incubated for 30 minutes in autologous serum. A similar reduction in chemotaxis of normal PMNs occurred after incubation in RA sera. Preincubation of both RA and normal PMNs in RA serum (but not normal serum) resulted in an increase in the number of cells in which cell-associated immunoglobulins were demonstrable. This further reduction in RA PMN chemotaxis after exposure to autologous serum, together with an increase in immunoglobulin staining, may indicate selection of certain PMNs at the time of venepuncture due to cell margination. Such a selection process would call for a re-evaluation of previous studies of RA PMN function in relation to the disease process.     

Juvenile rheumatoid arthritis and bronchiolitis obliterans organized pneumonia

Diverse pleuropulmonary manifestations, including pleural effusion, rheumatoid nodulosis, fibrosis, obliterans brochiolitis, bronchiectasias, vasculitis, drug-induced lung disease, and obliterans bronchiolitis with organized pneumonia, have been described in patients with rheumatoid arthritis (RA). Bronchiolitis obliterans organized pneumonia (BOOP) is an uncommon condition described in patients with RA but not in juvenile RA (JRA). We described a patient with JRA who developed a BOOP.     

Juvenile rheumatoid arthritis with cardiac tamponade.

A 4-year-old girl with seronegative systemic juvenile rheumatoid arthritis developed acute cardiac tamponade. Pericardiocentesis and systemic corticosteroids resulted in complete recovery of the pericardial involvement. This was followed by complete remission of rheumatoid disease.     

Juvenile rheumatoid arthritis, juvenile chronic arthritis, and juvenile spondyloarthropathies.

Immunogenetics are supporting the marked heterogeneity of chronic arthritis in children. Thus DRw13-DRw18 and DQw6-DQw18 were associated with persistent pauciarticular disease in children with an early onset of disease. Several studies have shown DPw2 as an additional susceptibility factor in this subgroup. Standardization of diagnostic criteria for juvenile onset spondyloarthropathy and psoriatic arthritis is necessary; various studies are in progress, and although HLA-B27 provides the common marker, this may only apply to a small group of juvenile psoriatics who have spondyloarthropathy. In the management of juvenile rheumatoid arthritis, methotrexate in moderate doses has been shown to be superior to lower doses of methotrexate and placebo in controlling polyarthritis. Methotrexate may be of particular value in treating the polyarthritis that follows a pauciarticular onset. The possible value of sulfasalazine in a B27 group with persistent polyarthritis has been suggested. Highlights of corticosteroid therapy were intra-articular injections, particularly in pauciarticular disease, the suggestion that deflazacort has a calcium sparing effect, and the possible role of intravenous methylprednisone in the management of severe disease.