Angiogenesis in rheumatoid arthritis: pathogenic and clinical significance

In summary, angiogenesis, the formation of new blood vessels, is important in leukocyte extravasation and thus the pathogenesis of RA. The outcome of neovascularization highly depends on the imbalance between angiogenic and angiostatic mediators produced in the rheumatoid synovium. Therefore, angiogenesis research is important for the understanding of the pathogenesis of inflammatory arthritis. In addition, existing and potential angiostatic drugs may be useful for future therapy of RA.     

The significance of fibronectin in cryoprecipitation in rheumatoid arthritis and other diseases

Fibronectin, a glycoprotein produced by mesenchymal cells, was present in 11 of 16 plasma cryoprecipitates and 12 of 14 synovial fluid (SF) cryoprecipitates. In some SF cryoprecipitates it was the major protein component. Fibronectin levels were related to the development of serum turbidity in the cold and fibronectin was involved in the development of cold turbidity induced by some charged polysaccharides in plasma, serum, and SF. It is suggested that fibronectin, which is synthesized by vascular endothelial cells and synovial lining cells, is involved in the development of some cryoprecipitates in patients with rheumatoid arthritis and other diseases.     

The diagnostic significance of certain histopathologic changes for rheumatoid arthritis

As a practical and unequivocally pathognomonic sign for RA could serve a histopathologic change which both displays a conspicuous morphologic distinctiveness and occurs with an overwhelming frequency in RA versus an insignificant or absent frequency in other categories of synovitis. Such postulates were not fulfilled by any of the herein described histopathologic changes. Therefore, no absolutely or indisputably pathognomonic feature may be asserted for RA, although it must be recognized that highly suggestive or indicative significance has to be acknowledged for some of the herein listed histopathologic changes of the synovial membrane.     

Corticosteroid prescribing in rheumatoid arthritis and psoriatic arthritis

Embryos from certain mouse strains are arrested at the 2-cell stage in cell culture ('2-cell block'), whereas those from other strains develop to the blastocyst stage under the same conditions. It was previously shown that blocking embryos can be rescued in culture by aggregation with an excess of 2-cell stages of a non-blocking strain such as CBA x C57BL/6 F2. Here we have employed a LacZ transgene in a blocking strain (NMRI) to follow the fate of rescued blastomeres up to the blastocyst stage. We found that rescued blastomeres can participate in both inner cell mass and trophoblast formation, thus completely overcoming the 2-cell block.     

Tumors in rheumatoid arthritis

Benign (bTu) and malignant tumours (mTu) were studied in a randomised autopsy material of 161 patients with rheumatoid arthritis (RA). The tissue specimens were fixed in 8% formaldehyde solution at pH 7.6 and embedded in paraffin. The tumours were diagnosed histologically and confirmed by immunohistochemical methods. Five benign (3.1%), and thirteen malignant tumours (8.1%) found observed in 18 (11.2%) of 161 cases. There was no significant difference between laboratory parameters of patients with malignant tumours and without tumours. One benign (0.62%) and seven malignant (4.35%) tumours led to death in 8 (4.97%) of 18 cases altogether. Neoplasms were detected clinically in 8 of 18 cases (44.4 rel%). None of tumorous patients received immunosuppressive treatment and only five had gold (Tauredon) therapy. Paraneoplastic syndromes with rheumatoid complaints may be excluded by the onset and duration of RA and tumours. Benign neurogenic tumours and malignant bronchioloalveolar carcinoma were frequently associated with RA not treated by immunosuppressive drugs. Our data do not support the assumption of a high risk of malignant lymphomas associated with RA treated with immunosuppressive therapy.     

Osteoporosis in rheumatoid arthritis

Patients with rheumatoid arthritis (RA) develop both periarticular and generalized osteoporosis. Periarticular osteopenia in appendicular bones occurs early in the course of RA and is one of the earliest radiological signs of RA. An uncoupled state in bone resorption-formation linkage, contributes to the development of periarticular osteopenia and it might be mediated through an increased productions of cytokines and prostaglandins by synovium and bone marrow. Accordingly, early suppression of rheumatoid synovitis is necessary for the prevention of periarticular osteopenia. Generalized osteoporosis is also common in RA and leads to increased risk of fractures. Generalized osteoporosis considered to be multifactorial and factors contributing to lumbar osteoporosis might be different from those to loss of appendicular bones, such as femur and radius. Corticosteroids and menopausal state are important risk factors for lumbar osteoporosis. Rheumatoid activity and reduced physical activity are also important determinants. According to the previous studies, however, the influence of functional impairment is more prominent in the femoral BMD compared to spinal BMD. In addition to control of RA and maintenance of physical activity, hormone replacement therapy (HRT) and bisphosphonate are possible agents for the treatment of osteoporosis in RA patients, especially postmenopausal women.     

Infection in rheumatoid arthritis

Sepsis is an unusually common cause of illness and death in RA. All sorts of infections occur, but pyarthrosis produces exceptional problems. Clinically, pyarthrosis, empyema, and purulent pericarditis mimic bland rheumatoid effusions. Aspiration of the attendant effusions is the only reliable diagnostic procedure. Subcutaneous nodules on the sacrum and back are easily overlooked. Necrosis and ulceration of these nodules may provoke septicemia. Those with Felty's syndrome do not uniformly have problems with recurrent infection. Splenectomy may not benefit such patients. The belief that corticosteroids cause increased infections in rheumatoid patients is not totally justifiable at present. Steroids can, however, disguise underlying sepsis and hamper proper diagnosis.     

Osteoporosis in rheumatoid arthritis

In cases of rheumatoid arthritis, osteoporosis may be local or general. The aetiology is multifactorial. Reduced bodily function, synovial inflammation, steroids and menopause are important risk factors. Studies have shown that, in cases of primary osteoporosis, bone mineral density measurements in the distal radius may predict risk of fracture at other sites, such as the neck of the femur and the dorsal vertebrae. Such a connection is not found for rheumatoid arthritis. Bone density measurements in the distal radius may overestimate the risk of fractures due to localised periarticular osteoporosis. Overall bone quality is assumed to be poorer, however, in patients with rheumatoid arthritis, leading to higher risk of fracture than the bone mineral density measurements seem to show. Data are lacking on the effect of antiresorptive drugs on this condition. Treatment with oestrogen and the bisphosphonate pamidronate has been shown to increase bone mineral density. Data are lacking on fractures. As shown in the case of primary osteoporosis, decreased risk of fracture is to be expected also in patients with secondary osteoporosis.     

Osteomalacia in rheumatoid arthritis

The influence of duration of vascular occlusion upon the reactive hyperemic response in human cutaneous tissue was studied in 6 subjects. Blood flow in cutaneous tissue was measured dorsally on the distal phalanx of the second finger by the local 133Xenon washout technique. Post-occlusive blood flow, calculated from the steepest part of the 133Xenon washout curve just after release of vascular occlusion, reached a maximum value when duration of vascular occlusion was 12 min. However, excess cumulative blood flow, i.e. the integrated blood flow during reactive hyperemia minus integrated pre-ischemic blood flow for a period corresponding to the duration of the reactive hyperemic response, increased with increasing duration of vascular occlusion from 3 to 24 min. Fractional repayment, i.e. excess cumulative blood flow divided by pre-ischemic blood flow times duration of vascular occlusion, was not correlated significantly to duration of vascular occlusion. However, there was a significant inverse correlation between fractional repayment and pre-occlusive blood flow, indicating that, besides metabolic factors, pre-ischemic blood flow in cutaneous tissue is influenced by other factors, such as heat regulation.     

Pregnancy and rheumatoid arthritis

Amelioration of rheumatoid arthritis (RA) occurs in about three quarters of pregnancies. Most women who improve experience initial relief in the first trimester. RA almost invariably recurs within 3 to 4 months of delivery. The effect of pregnancy upon the risk of first developing RA is similar in some respects but also differs from that observed in women with established disease. Analogous to women with established disease, the chance of a woman first developing RA is significantly reduced during pregnancy but increased in the first year post partum; thereafter risk is decreased. There is no indication of any adverse effects of RA on pregnancy outcome. Although limited, some medications can be used during pregnancy and during lactation without jeopardizing the well-being of the fetus.     

Juvenile rheumatoid arthritis

JRA is a multisystem disease characterized by exacerbations and remissions. Recognition of the three modes of onset can important in early diagnosis, identification of extra-articular manifestations, and prognosis. This is a chronic illness that requires consideration of the whole patient, his family, and his place in society, both in the present and in the future. With a positive, comprehensive approach and an awareness of the pitfalls of seeking immediate relief, the physician can help to assure a good functional outcome.