Macrophage accumulation, and the expression of chemokines and MMPs in synovial tissue occur in early RA. Targeting chemokines which play a role in the migration of macrophages into the joints may be of therapeutic benefit in RA patients.
Autoimmune inflammatory rheumatic diseases (AIIRD), such as rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis are often complicated by infection, which results in significant morbidity and mortality. The increased risk of infection is probably due to a combination of immunosuppressive effects of the AIIRD, comorbidities and the use of immunosuppressive conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) and more recently, targeted synthetic DMARDs and biologic DMARDs that block specific pro-inflammatory enzymes, cytokines or cell types. The use of these various DMARDs has revolutionised the treatment of AIIRD. This has led to a marked improvement in quality of life for AIIRD patients, who often now travel for prolonged periods. Many infections are preventable with vaccination. However, as protective immune responses induced by vaccination may be impaired by immunosuppression, where possible, vaccination may need to be performed prior to initiation of immunosuppression. Vaccination status should also be reviewed when planning overseas travel. Limited data regarding vaccine efficacy in patients with AIIRD make prescriptive guidelines difficult. However, a vaccination history should be part of the initial work-up in all AIIRD patients. Those caring for AIIRD patients should regularly consider vaccination to prevent infection within the practicalities of routine clinical practice.
Objective To investigate the effects of intraarticular glucocorticoid treatment on macrophage infiltration, the expression of the chemokines monocyte chemoattractant protein 1 (MCP‐1) and macrophage inflammatory protein 1α (MIP‐1α), and the expression of matrix metalloproteinases 1 and 3 (MMPs 1 and 3) and their inhibitors, the tissue inhibitors of metalloproteinases 1 and 2 (TIMPs 1 and 2), in osteoarthritis (OA) synovial membranes. Methods Forty patients underwent arthroscopic biopsy before and 1 month after intraarticular injection of glucocorticoids. Twenty‐one patients received 120 mg of methylprednisolone acetate (Depo‐Medrol; Upjohn, Kalamazoo, MI), and 20 patients received placebo (1 patient received placebo in 1 knee and methylprednisolone acetate in the other). Immunoperoxidase staining for the expression of CD68, MCP‐1, MIP‐1α, MMP‐1, MMP‐3, TIMP‐1, and TIMP‐2 was performed, and the immunostaining was quantified by color video image analysis. Results CD68, MCP‐1, MIP‐1α, MMP‐1, MMP‐3, TIMP‐1, and TIMP‐2 immunostaining was observed in all synovial membranes. Intraarticular glucocorticoid treatment was associated with a small (30%) but statistically significant (P = 0.048) reduction in CD68+ macrophage staining in the synovial lining layer, but there was no change in the CD68 expression in the synovial sublining layer. No significant differences were observed for MCP‐1, MIP‐1α, MMP‐1, MMP‐3, TIMP‐1, and TIMP‐2 immunostaining in the synovial lining or sublining layers. Conclusion Intraarticular glucocorticoids may reduce CD68+ macrophage infiltration into the synovial lining layer, but not the expression of MCP‐1, MIP‐1α, MMP‐1, MMP‐3, TIMP‐1, and TIMP‐2 in the synovial membrane, in patients with OA.
We report three patients who developed antineutrophil cytoplasmic autoantibody (ANCA)-associated crescentic glomerulonephritis, two of whom showed clinical features of limited scleroderma and one whose results of serological tests were suggestive of limited scleroderma without cutaneous features. All had anticentromere antibodies and antimyeloperoxidase antibodies. No patient showed the features of typical scleroderma renal crisis such as accelerated hypertension or microangiopathy. Our patients were normotensive at the time of onset of renal failure, and the clinical picture was characterised by only modest features of limited scleroderma. All three patients had crescentic glomerulonephritis at various stages of chronicity. One patient responded to immunosuppressive therapy with improvement in renal function; the other two patients rapidly developed end-stage renal failure. These patients and others recently described may represent a newly described form of scleroderma renal disease.
Rheumatoid arthritis (RA) affects approximately 1% of the population and is a chronic inflammatory joint disease resulting in joint destruction, increased morbidity and mortality. Although the aetiology of this disease is unknown, the pivotal role played by cytokines and degradative enzymes in mediating inflammation and joint destruction, particularly early in the disease process, has been the focus of recent literature and will be the focus of this review. Up until recently, studies on early RA were limited as there was an inherent delay in patients reaching the rheumatologist's care and initial diagnostic confusion may have compounded these problems. In particular, the observation that early intervention improves outcome, has driven the study of early RA. It is difficult to define early RA but most studies have defined this as disease duration of less than 12 months from symptom onset. Clearly, it is important to study the synovial membrane in early disease, in particular to try and answer the important questions: (1) What are the earliest changes to occur in the RA synovium? (2) Can we distinguish RA on the basis of synovial membrane pathology? (3) Can synovial immunopathology predict outcome? (4) What is the role of arthroscopic biopsy in early RA?
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