Signs and symptoms of HCV infection and RA can overlap and may include common manifestations, such as arthralgias, and less common manifestations, such as vasculitis. In a patient with HCV infection who has arthralgias and is rheumatoid factor (RF)–positive, the clinician must determine whether the arthralgias are due to HCV or to RA. The treatment of these 2 clinical entities is completely different. While those with HCV-related arthralgias do not typically have a destructive type of arthritis, RA can be quite destructive and disabling.

When musculoskeletal symptoms occur in HCV, they typically present as low-grade arthralgias. Less commonly, HCV may be associated with inflammatory joint disease. RA-like HCV-related arthropathy can be clinically indistinguishable from RA itself. Because the classic clinical picture of RA may not be extremely helpful in the differential diagnosis, other diagnostic tools, such as the detection of serologic abnormalities in patients with RA, can be helpful in differentiating between these 2 disorders. Anti-cyclic citrullinated peptide (anti-CCP) antibodies are fairly pathognomonic for RA, but the presence of RF is not. RF can be positive in a number of other connective tissue diseases (eg, Sjögren’s syndrome) and infections (eg, parvovirus B19, HCV). Anti-CCP antibody is positive in many patients with RA, but it is negative in those RF-producing patients who have arthralgias from HCV.

As an extraarticular manifestation of RA, vasculitis is diminishingly rare in the modern treatment era. In HCV, circulating mixed cryoglobulins may be present along with the arthralgias and they may precipitate the development of cryoglobulinemic vasculitis, which is also rare. Patients with chronic HCV infection can develop small-vessel or medium-vessel vasculitis, although vasculitis is present in less than 5% of HCV-infected individuals. Finally, with respect to the patient who has RA and concomitant HCV infection, anti–tumor necrosis factor therapy is considered safe, although treatment should be individualized by the rheumatologist in collaboration with the hepatologist to minimize complications.