Many rheumatic conditions and other chronic inflammatory processes also may produce rheumatoid factors. An incomplete list includes subacute bacterial endocarditis, malaria, syphilis, tuberculosis, hepatitis, leprosy, leishmaniasis, sarcoidosis, and infectious mononucleosis. Thus, the presence of rheumatoid factor, especially in low titer, is far from diagnostic for rheumatoid arthritis. Furthermore, with increasing age, people with no clinical illness may have rheumatoid factor. Statistically, patients with rheumatoid arthritis who have high titer rheumatoid factor are more likely to have severe disease and systemic involvement than other patients.
High titers correlate with presence of rheumatoid nodules, and low synovial fluid complement.
Rheumatoid factor can be detected in synovial fluid, but contributes little more than a positive serum test. Some rheumatoid factors may behave as cryoglobulins.