Rheumatic disease and the Australian aborigine.
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OBJECTIVE: To document the frequency and disease phenotype of various rheumatic diseases in the Australian Aborigine. METHODS: A comprehensive review was performed of the archaeological, ethnohistorical, and contemporary literature relating to rheumatic diseases in these indigenous people. RESULTS: No evidence was found to suggest that rheumatoid arthritis (RA), ankylosing spondylitis (AS), or gout occurred in Aborigines before or during the early stages of white settlement of Australia. Part of the explanation for the absence of these disorders in this indigenous group may relate to the scarcity of predisposing genetic elements, for example, shared rheumatoid epitope for RA, B27 antigen for AS. In contrast, osteoarthritis appeared to be common particularly involving the temporomandibular joint, right elbow and knees and, most probably, was related to excessive joint loading in their hunter gatherer lifestyle. Since white settlement, high frequency rates for rheumatic fever, systemic lupus erythematosus, and pyogenic arthritis have been observed and there are now scanty reports of the emergence of RA and gout in these original Australians. CONCLUSION: The occurrence and phenotype of various rheumatic disorders in Australian Aborigines is distinctive but with recent changes in diet, lifestyle, and continuing genetic admixture may be undergoing change. An examination of rheumatic diseases in Australian Aborigines and its changing phenotype may lead to a greater understanding of the aetiopathogenesis of these disorders. (+info)
Diagnostic evaluation of classification criteria for rheumatoid arthritis and reactive arthritis in an early synovitis outpatient clinic.
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OBJECTIVE: To evaluate the diagnostic performance of classification criteria for rheumatoid arthritis (RA) and reactive arthritis (ReA) in an early synovitis outpatient clinic. METHODS: In a prospective two year survey consecutive patients with early synovitis of less than one year duration were documented using a standardised registry and were classified after an expert diagnosis. Of a total of 320 patients 39 (19%) were diagnosed as having RA, 24 (11%) patients had ReA, 117 (54%) patients did not have an unequivocal diagnosis, and were considered as undifferentiated arthritis. RESULTS: The retrospective application of the revised 1987 ACR criteria for the classification of RA in this data set revealed a sensitivity of 90% and a specificity of 90%. The positive predictive value was 0.67, the negative predictive value 0.98. Similarly, the criteria for ReA of the French Society of Rheumatology (FSR) showed a sensitivity of 80% and a specificity of 90% with a positive predictive value of 0.55 and a negative predictive value of 0.97. Both criteria sets had a satisfying likelihood ratio of 9 and 10, respectively. CONCLUSION: Both the 1987 ACR criteria for RA and the criteria of the FSR for ReA have a reasonable diagnostic validity in patients with early synovitis, including a large portion of undifferentiated arthritis. (+info)
Prospective six year follow up of patients withdrawn from a randomised study comparing parenteral gold salt and methotrexate.
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OBJECTIVE: To confirm the impression of a better outcome of patients withdrawn from parenteral gold salt therapy compared with those withdrawn from methotrexate. METHODS: Patients with early, active, and erosive RA were randomised for a double blind trial to receive either weekly 15 mg intramuscular methotrexate or 50 mg goldsodiumthiomalate. If the drug had to be withdrawn because of side effects treatment was continued with the other drug in still active disease. Patients with insufficient response were treated with a combination of both drugs. All patients were followed up by an extended clinical and radiographic evaluation. RESULTS: 64 patients each were allocated to methotrexate and gold treatment. After 72 months a complete record was available for 88% of patients. Within the first 36 months 38 patients withdrew from gold treatment (95% because of side effects) and 23 patients withdrew from methotrexate (57% because of side effects). A significant 40% to 70% improvement of all parameters (erythrocyte sedimentation rate, C reactive protein, swollen and tender joints, radiological progression) compared with baseline was observed in patients completing their randomised treatment with gold or methotrexate. The same improvement over three years was seen in patients who withdrew from gold treatment, while patients withdrawing from methotrexate experienced a deterioration of their disease. CONCLUSION: Withdrawals represent the majority of patients in long term drug trials. Patients with early RA stopping gold because of side effects show almost the same sustained improvement as patients continuing gold or methotrexate. Patients withdrawn from methotrexate experience a reactivation of their disease. (+info)
Does sulphasalazine cause drug induced systemic lupus erythematosus? No effect evident in a prospective randomised trial of 200 rheumatoid patients treated with sulphasalazine or auranofin over five years.
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BACKGROUND: Sulphasalazine (SSZ) has been reported to cause drug induced systemic lupus erythematosus (SLE), but diagnosis of this complication in the context of rheumatoid arthritis (RA) is difficult. OBJECTIVE: To determine prospectively: (1) if patients become seropositive for antinuclear antibodies (ANA) during prolonged treatment with SSZ without clinical evidence of SLE; (2) if ANA positive patients develop more adverse reactions than ANA negative patients; (3) if drug induced SLE was identified in this cohort. METHODS: 200 patients enrolled in a randomised prospective trial of SSZ and auranofin (AUR) were followed up for five years. Baseline and annual ANA results were collected along with information on drug toxicity and reasons for discontinuation of treatment. RESULTS: Over five years 24 patients stopped taking SSZ and 49 AUR because of side effects. Of the features common to SLE, rash developed in nine SSZ patients and 11 AUR treated patients and mouth ulcers in three and four patients respectively. Six SSZ treated patients and three treated with AUR developed leucopenia, which promptly resolved with drug withdrawal. No adverse event was ascribed to drug induced SLE. Of the 72 SSZ treated patients who were ANA negative or weakly positive at outset, 14 (19%) became strongly ANA positive compared with 11 (14%) of 80 AUR patients. Patients ANA positive at baseline or who became ANA positive were not more likely to develop drug toxicity or to withdraw from treatment than those ANA negative throughout. CONCLUSION: ANA positivity is common in patients with RA, but the presence or development of ANA did not increase the likelihood of withdrawing from treatment. No case of drug induced SLE was seen over five years in this study. (+info)
Anti-heat shock protein 70 kDa and 90 kDa antibodies in serum of patients with rheumatoid arthritis.
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OBJECTIVES: Stress proteins (HSPs) are highly conserved immunodominant antigens found in various species. The purpose of this study was to assess the prevalence and prognostic significance of antibodies to HSC 70 kDa and HSP 90 kDa in three groups of patients with longstanding rheumatoid arthritis (RA) defined based on the severity of articular erosions. METHODS: 73 patients with longstanding (> 6 years) RA whose HLA-DR genotype was known were divided in three groups according to Larsen's score and compared with 47 recent onset (<1 year) RA patients and with control groups composed of patients with other inflammatory diseases (n=137) or of normal controls (n=48). IgGs and IgMs to HSC 70 kDa and HSP 90 kDa were determined using an ELISA with purified bovine HSC 70kDa or HSP 90 kDa. RESULTS: Concentrations of IgGs and IgMs to HSC 70 were significantly increased in 41.1% and 42.5% of longstanding RA patients, respectively. Corresponding figures for IgGs and IgMs to HSP 90 were 39.7% and 56%. IgMs to HSC 70 and HSP 90 were less frequent in recent onset RA (19% and 13% respectively). Among the groups with other inflammatory diseases, only the MCTD group exhibited high frequencies of IgGs to HSC 70 (80%) and HSP 90 (85%). DRB1*0401 positive RA patients (n=23) were not more likely to have increased concentrations of antibodies to HSC 70 kDa or HSP 90 kDa than other RA patients (DR4 positive but DRB1*0401 negative, or DR1 positive, n=31; or negative for both DR4 and DR1, n=14). IgGs to HSP 90 kDa were significantly more frequent (p<0.05) in longstanding RA patients whose Larsen's score was 4 or more (57%) than in those whose Larsen's score was 2 or 3 (39.4%) or less than 2 (16%). No associations were found between Larsen's score and IgGs or IgMs to HSC 70 kDa or IgMs to HSP 90 kDa. A significant correlation was demonstrated between IgGs to HSP 90 kDa and two other serological markers for RA, rheumatoid factor, and anti-Sa antibody; there were no correlations with antikeratin antibody, antiperinuclear factor, or anti-RA 33. CONCLUSION: IgGs to HSP 90 kDa are most common in longstanding RA patients with articular erosions, suggesting that they may be related to the articular prognosis in RA (+info)
Macrophage inflammatory protein 1 alpha expression by synovial fluid neutrophils in rheumatoid arthritis.
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OBJECTIVE: To determine the contribution made by synovial fluid (SF) neutrophils to the augmented expression of macrophage inflammatory protein 1 alpha (MIP-1alpha) in rheumatoid arthritis (RA). METHODS: Neutrophils were isolated from samples of SF from RA patients and peripheral blood (PB) samples from RA patients and healthy controls. Cell associated MIP-1alpha was visualised immunohistochemically, and cell associated MIP-1alpha as well as MIP-1alpha secreted into the SF was assayed by ELISA. Steady state expression of MIP-1alpha mRNA was assessed by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Freshly isolated SF neutrophils contained significantly higher concentrations of both MIP-1alpha protein and its transcript than PB neutrophils from either RA patients or healthy controls; incubation in the absence or presence of tumour necrosis factor alpha for 24 hours resulted in a significant increase in MIP-1alpha secretion by RA SF neutrophils compared with neutrophils obtained from either normal PB or RA PB; and expression of MIP-1alpha by SF neutrophils was well correlated with both RA disease activity and SF mononuclear cell (MNC) counts. CONCLUSION: Expression and secretion of MIP-1alpha by SF neutrophils may be indicative of local and systemic inflammation in RA. Moreover, this C-C chemokine may contribute to the recruitment of MNCs from the bloodstream into synovial joints and tissues. (+info)
IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis.
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IL-17 is a newly discovered T cell-derived cytokine whose role in osteoclast development has not been fully elucidated. Treatment of cocultures of mouse hemopoietic cells and primary osteoblasts with recombinant human IL-17 induced the formation of multinucleated cells, which satisfied major criteria of osteoclasts, including tartrate-resistant acid phosphatase activity, calcitonin receptors, and pit formation on dentine slices. Direct interaction between osteoclast progenitors and osteoblasts was required for IL-17-induced osteoclastogenesis, which was completely inhibited by adding indomethacin or NS398, a selective inhibitor of cyclooxgenase-2 (COX-2). Adding IL-17 increased prostaglandin E2 (PGE2) synthesis in cocultures of bone marrow cells and osteoblasts and in single cultures of osteoblasts, but not in single cultures of bone marrow cells. In addition, IL-17 dose-dependently induced expression of osteoclast differentiation factor (ODF) mRNA in osteoblasts. ODF is a membrane-associated protein that transduces an essential signal(s) to osteoclast progenitors for differentiation into osteoclasts. Osteoclastogenesis inhibitory factor (OCIF), a decoy receptor of ODF, completely inhibited IL-17-induced osteoclast differentiation in the cocultures. Levels of IL-17 in synovial fluids were significantly higher in rheumatoid arthritis (RA) patients than osteoarthritis (OA) patients. Anti-IL-17 antibody significantly inhibited osteoclast formation induced by culture media of RA synovial tissues. These findings suggest that IL-17 first acts on osteoblasts, which stimulates both COX-2-dependent PGE2 synthesis and ODF gene expression, which in turn induce differentiation of osteoclast progenitors into mature osteoclasts, and that IL-17 is a crucial cytokine for osteoclastic bone resorption in RA patients. (+info)
Regulation of inflammatory responses by oncostatin M.
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Oncostatin M (OM) is a pleiotropic cytokine produced late in the activation cycle of T cells and macrophages. In vitro it shares properties with related proteins of the IL-6 family of cytokines; however, its in vivo properties and physiological function are as yet ill defined. We show that administration of OM inhibited bacterial LPS-induced production of TNF-alpha and lethality in a dose-dependent manner. Consistent with these findings, OM potently suppressed inflammation and tissue destruction in murine models of rheumatoid arthritis and multiple sclerosis. T cell function and Ab production were not impaired by OM treatment. Taken together these data indicate the activities of this cytokine in vivo are antiinflammatory without concordant immunosuppression. (+info)