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Nonsteroidal anti-inflammatory drugs (NSAIDs) are now the most commonly prescribed agents in the treatment of rheumatic diseases because of their analgesic and anti-inflammatory properties. The major mechanism whereby NSAIDs achieve their anti-inflammatory effects has been shown to be the inhibition of prostaglandin (PG) biosynthesis. An increasing number of patients have developed serious complications from NSAIDs. This inhibition is documented to be a cause of adverse reactions of NSAIDs. Among these complications, we reviewed and discussed gastrointestinal (GI) and renal disorders in this symposium. Of 1008 Japanese RA patients taking NSAIDs, gastric ulcer was noticed in 15.5% of the cases. The high prevalence of GI injury in RA patients has been esteemed to be responsible for the use of NSAIDs. The following 4 types of drugs are known to be useful for prevention of NSAIDs-related GI mucosal damage：histamine-receptor antagonist；gastric acid pump inhibitor；barrier agents；and PG analogue. A PG analogue, misoprostol, was to be the most effective agent. Furthermore, NO-releasing NSAIDs, which were recently developed, may be able to reduce adverse reactions of GI tract. NSAIDs may cause renal disorders by different mechanisms, including reversible renal hypoperfusion, acute tubular necrosis, or acute tubulointerstitial nephritis with or without nephrotic syndrome. The long-term treatment with NSAIDs may produce a subclinical renal dysfunction. Furthermore, severe renal dysfunction are likely to develop in patients with poor perfusion. Irreversible renal failure may also develop in patients receiving other medications that may have contributed to renal dysfunction. Selective cyclooxygenase-2 inhibitors such as etodolac have shown the lower incidence of adverse reactions in GI tract and kidney than other conventional NSAIDs. Misoprostol can also minimize NSAIDs-induced renal dysfunction without affecting pain control.

Osteoporosis is now recognized as one of the major problems of female SLE patients. We measured bone mineral density (BMD) in 54 female SLE patients using dual energy X-ray absorptiometory, and studied the relationship between BMD and clinical parameters or steroid and vitamine D treatment. There was an inverted relation between patient's age and BMD. BMD decreased remarkably in the age of forties and fifties. In the series study of BMD, both patients treated with vitamine D metabolites (group A) and those of untreated (group B) revealed no difference between initial and last BMD, The initial BMD of group A was significantly lower than that of group B. It means that vitamine D methabolites were administrated in patient showing lower DEXA. No remarkable difference were detected in serum biochemical parameters, creatinine clearance and urinary findings between two groups. BMD was not different between both nephrotic and non-nephrotic patients or between those with or without aseptic necrosis of femaral head. Further prospective controlled studies showed be performed to confirm the efficiency of vitamine D metabolites.

Comparative studies of clinical, laboratory and immunological findings were performed for 134 rheumatoid arthritis (RA) patients in relation to several extra-articular features. There were 22 cases of malignant RA (MRA) or RA with interstitial pneumonia. The titers of rheumatoid factor (RF) determined by enzyme linked immunosorbent assay were significantly higher in sera from these RA patients than in sera from RA patients without extra-articular features. Seventeen RA patients were complicated by secondary amyloidosis. In this group, proteinuria and impairment of renal function were observed frequently. Concurrence of RA and other collagen vascular diseases were observed in 18 patients. In this group, hypocomplimentemia and hypergammaglobulinemia were observed frequently. RA with biopsy-proven renal disease were observed in 30 patients. Laboratory results of this group revealed characteristic findings, namely lower concentrations of CRP and RF compared with those of other groups. These results suggest that inflammatory and immunological mechanisms may not have any major role in the pathogenesis of nephropathy in patients with RA, contrary to their role in other extra-articular manifestations experienced in MRA patients.

Systemic lupus erythematosus (SLE) is characterized by production of many autoantibodies. The clinical significance of the autoantibodies, especially anti-DNA antibody and antiphospholipid antibodies, was discussed in this paper. Anti-dsDNA antibody is highly specific for SLE and rarely seen in a significant titer in other rheumatic diseases. This antibody is useful for assessing desease activity. It can bind to several cellular components or bacterial polysaccharides, which suggest that the restricted anti-DNA antibody may account for the serological abnormalities and the tissue injury in SLE. Anti-phospholipid antibodies include BFP-STS, lupus anticoagulant, anti-cardiolipin antibody and anti-phosphatidyl serine antibody. These antibodies had a significant correlation with fetal wastage, thrombocytopenia, CNS lupus and thrombosis. We observed 3 patients who had successful pregnancies after anti-phosphatidyl serine antibody reduced to normal level. Anti-phpsphatidyl serine antibody is surely useful for the management of pregnancy in lupus patients.

Membrane plasmapheresis is a new therapeutic tool to control patients with autoimmune and metabolic disorders. Double filtration plasmapheresis, in which two membrane filters with different pore size are utilized to selectively remove pathogenic macromolecules in plasma, has been found to be safe and efficient system of membrane plasmapheresis for various autoimmune diseases. In Niigata University Hospital, 30 patients with autoimmune and hyperlipidemic diseases have been treated with double filtration plasmapheresis and 21 patients with metabolic diseases have been done with single membrane plasma exchange using fresh-frozen plasma. We have observed no major side effects in this treatment. Plasmapheresis presently is an appropriate symptomatic treatment, and future research must undertake to clarify the pathogenic factors which should be removed from the blood.