Parvovirus B19 was identified in human serum in the mid-1970s (2). However, its disease manifestations have been recognized since the 1800s, with the initial description of “fifth disease” or erythema infectiosum in children (3). The classic forms of parvovirus B19 infection occur at either the viremic stage (transient aplastic crisis and pure red cell aplasia) or the postviremic stage (erythema infectiosum and arthropathy; 2). While children commonly present with the classic “slapped cheek” and reticular rash of erythema infectiosum, rash is usually absent or subtle in adults (1). Conversely, arthralgias or arthritis is far more common in adults with acute infections (4). The classic arthritis begins precipitously in a few joints, spreads rapidly in 24 to 48 hours, and is characterized by severe, prolonged morning stiffness.

Patients tend to present with a low temperature. A lacy rash, most commonly present in the extremities, can be found. Tender, swollen joints are commonly seen, but no deformities are present. Both small- and medium-size joints are predominantly affected usually in a symmetrical fashion (1). Axial joints are spared.

Viremia is evident by 5 to 6 days postexposure, with a peak at 8 to 9 days. The virus clears quickly, and IgM is present by days 10 to 12 and may persist for 2 to 3 months (2). Serum of infected patients can show transient autoantibodies, including, but not limited to, ANA, RF, and anti-DNAs (4). Diagnosis therefore relies on serum IgM antibodies to parvovirus B19, with or without IgG and demonstrable parvovirus DNA.

Treatment is supportive, with nonsteroidal anti-inflammatory drugs (NSAIDs) as needed for pain and inflammation. Intravenous immunoglobulin has been used in cases of pure red cell aplasia in immunocompromised patients, but it is not recommended in arthritis (4).

Acute arthritis resolves within weeks although, uncommonly, cases have persisted for months. Whether parvovirus B19 infection causes a chronic arthritis remains controversial (4), as does its possible association with RA and other inflammatory arthropathies. Some studies have found ongoing B19 DNA in serum, bone marrow, and synovium of patients with chronic arthritis and/or RA, but they have been found in healthy controls as well, making a determination of the cause difficult (1,2,4,5,6).

Hepatitis C (HCV) is a single-stranded RNA Flavivirus. It is estimated that greater than 170 million people worldwide are infected with the virus (7). Parenteral infection occurs most commonly, often in the setting of intravenous drug use. Transmission in health care settings has become rare in developed countries since routine testing of blood products began in the early 1990s; however, occasional cases continue to be reported (7). Following acute infection with HCV, 74% to 86% of patients develop persistent viremia and 15% to 20% of these patients with chronic infection develop cirrhosis (7), which can progress to hepatocellular carcinoma and end-stage liver disease.

Extrahepatic manifestations of HCV infection are varied, with joint pain being a common one. Studies estimate that 9% to 29% of all patients with HCV complain of arthralgias, while 2% to 4% of patients have arthritis (1,8). True inflammatory arthritis appears to manifest in four distinct ways: (1) relating directly to HCV infection (2) as a sign of mixed cryoglobulinemia (3) coexisting, but separate rheumatic disease (4) occurring rarely secondary to therapy for HCV (4). As therapy-related arthritis is exceedingly rare, further discussion of 1 to 3 follows.

Patients can develop an inflammatory arthritis directly related to HCV, which occurs in fewer than 5% of patients (4). Physical examination reveals evidence of synovitis of small joints in a symmetrical pattern.

Essential mixed cryoglobulinemia is associated with HCV infection, and symptoms include purpura, glomerulonephritis, lymphadenopathy, skin ulcers, and peripheral neuropathy. Many patients complain of arthralgias; however, less than 10% develop frank arthritis (4). The classic triad is described as that of purpura, glomerulonephritis, and arthralgias. Physical examination seldom reveals evidence of synovitis or deformity; skin examination shows palpable purpura most frequently in the lower extremities.