Seronegative rheumatoid arthritis. Fact or fiction?

Patients with clinical features of rheumatoid arthritis (RA) but negative rheumatoid factor (RF) present a diagnostic challenge. The seronegative spondyloarthropathy (SNSA) syndromes, previously believed to be "rheumatoid arthritis variants," eg, Reiter's syndrome and psoriatic arthritis, are now considered to be genetically separate from RA and have been shown to be closely associated with HLA-B27. This syndromic discrimination has raised question as to the validity of RF negative RA (ie, seronegative RA). Demographic, clinical, and roentgenologic features of seronegative RA and SNSA are compared. Also, more common diagnoses that may stimulate seronegative RA are outlined according to onset age of arthritis. Recent concepts of RF positivity and HLA-DR4 correlations are reviewed. Multiple unknown factors contribute to the currently recognized syndrome of RA. Its diagnosis continues to rest on an aggregate of host, clinical, immunologic, and radiologic features.