aPediatric Infectious Diseases, Combined Fellowship Training Program of Tulane University and Louisiana State University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA bDivision of Infectious Diseases, Department of Pediatrics, Louisiana State University Health Sciences Center, Children's Hospital, 200 Henry Clay Avenue, New Orleans, LA 70118, USA
Hepatitis C virus (HCV) infects approximately 3% of the world's population or 170 million people. In the United States, HCV represents the most common blood-borne chronic infection and is a leading cause of chronic liver disease. It is estimated that the overall prevalence of HCV in the United States is 1.8% or 3.9 million people with approximately 2.7 million people chronically infected [1,2]. These figures likely are an underestimate of the true incidence of the disease, however, because the infection may be clinically silent.
The main target of the virus is the hepatocyte and thus HCV primarily causes liver disease with cirrhosis and hepatocellular carcinoma being the most devastating consequence of long-term infection. In addition, HCV infection frequently is associated with various extrahepatic manifestations, such as arthritis and arthralgias, vasculitis, mixed cryoglobulinemia, glomerulonephritis, lichen planus, porphyria cutanea tarda, and B cell lymphomas . Depending on the population studied, some form of extrahepatic manifestation is observed in 24% to 74% of the patients [4-6] and they usually are seen during the chronic phase of the infection. Cacoub and colleagues  undertook a large, single-center evaluation of 1202 patients who had chronic HCV infection and described that 74% of them manifested extrahepatic symptoms, the risk factors being female sex, increasing age, and extensive liver fibrosis (suggesting that duration of infection or infecting genotype 1 also may represent risk factors, although these factors were not reported specifically). The mechanisms involved in extrahepatic manifestations are complex; HCV is known to be lymphotropic also  and persistent activation of immune cells leads to production of HCV-specific immunoglobulins with potential formation of immune complexes that may contribute to the various autoimmune and rheumatologic manifestations observed . Special
* Corresponding author.
E-mail address: [email protected] (R.E. Begue).
0891-5520/06/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.idc.2006.09.010 id.theclinics.com consideration in this respect should be given to cryoglobulins. Cryoglobulins are immunoglobulins of different isotypes that precipitate at temperatures less than 37°C and when deposited in small vessels can lead to vasculitis. There are three types of cryoglobulinemias: type I—monoclonal immunoglobulin IgG; type II (mixed)—polyclonal immunoglobulins IgG plus monoclonal immunoglobulins IgM, IgG, or IgA; and type III (mixed)— polyclonal IgG plus polyclonal IgM . Type II mixed cryoglobulinemia is the most common type seen in chronic HCV infection  and the immune complexes are composed of monoclonal IgM rheumatoid factor, polyclonal anti-HCV IgG, and HCV virions [9-11].
Although there are well-established extrahepatic immune and autoimmune manifestations of chronic HCV infection, including arthritis, it is unclear whether there is an arthritic syndrome particular to HCV infection. As far back as 1967, Pachas and Pinals  already described a nonerosive symmetrical polyarthritis seen in patients who had cirrhosis; it is unknown whether those patients indeed had HCV infection because the antibody assay would not be available for another two decades. Since then, several reports on the association of HCV and arthritis have been published, primarily in the rheumatology literature [13,14]; the interested reader is referred to those review articles. Here, we update and critically review the most recent literature to make the infectious diseases community aware of the issue and try to answer two important practical questions: (1) Is there a relationship between HCV infection and arthritis? (2) Does the co-occurrence of HCV infection and arthritis require modification of the treatment of either disease process?
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