What is seronegative rheumatoid arthritis?

Between classical, erosive, seropositive rheumatoid arthritis (RA) on one hand, and typical, axial ankylosing spondylitis (AS) on the other, there is a variety of seronegative polyarthritides, which are often difficult to diagnose, classify and also to distinguish from each other. During our studies of HLA antigens and their associations with rheumatic diseases, and particularly that of DR4 with RA, we became increasingly concerned with the problem of defining properly patients with seronegative RA. Both the statement of seronegativity with regard to rheumatoid factors (RF), the diagnosis of RA, and particularly the exclusion of cases of seronegative arthritis other than RA were difficult. We felt that such problems might explain the conflicting opinions as to the association between RF and HLA-DR4 in patients with RA. As a basis for discussing these problems, a set of criteria for RF seronegative RA are presented.