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Abstract
To provide and overview of the recent advances and controversies concerning the extra-articular complications of rheumatoid arthritis (RA), we have reviewed the English and Japanese literature with emphasis on articles published within the past 5 years. Disease modifying antirheumatic drugs (DMARDs) can control synovial inflammation but they may also affect various organs such as liver, lung, kidney and bone marrow. Thus, drug-induced side effects should be included in the differential diagnosis of extra-articular manifestations of RA. Other extra-articular manifestations are due to rheumatoid activity per se and seem to represent a group of diseases distinct from synovitis. High-dose steroids and immunosuppresive agents can generally induce remissions in patients with these manifestations but they do not decrease mortality. The association of HLA-DRB1 alleles with the severity of extra-articular manifestations is still debated.