LOCALIZATION OF HEPATITIS-C VIRUS IN CUTANEOUS VASCULITIC LESIONS IN PATIENTS WITH TYPE-II CRYOGLOBULINEMIA

Objective. To investigate the role of hepatitis C virus (HCV) in the p athogenesis of the cutaneous vasculitis in patients with type II cryog lobulinemia. Methods. Using in situ hybridization detection of HCV, we studied 6 test patients and various control subjects, Serum HCV was q uantitated, cryoglobulins were analyzed by column chromatography at 37 degrees C, and low-density lipoprotein (LDL) receptors on keratinocyt es were detected using LDL labeled with fluorescent dye. Results. In t he cutaneous vasculitic lesions from test patients, but not control su bjects, the HCV virion was found in association with IgM and IgG, HCV alone was detected in some vessel walls, and in skin and ductal epithe lium and vascular endothelium in inflamed, but not normal, skin, Cryog lobulins showed HCV, monomeric IgM, and monomeric IgG, with little or no immune complexes. The extent of the lesions correlated with levels of viremia, Up-regulation of LDL receptors on keratinocytes was detect ed in inflamed, but not normal, skin. Conclusion. HCV was present in t he cutaneous vasculitic lesions, most likely in complexes with IgM and IgG formed in situ, These findings and the correlation of the severit y of the rash with the level of viremia suggest that HCV plays a major role in the pathogenesis of cutaneous vasculitis in these patients an d strengthens the rationale for antiviral drug therapy, The presence o f HCV in keratinocytes and ductal epithelial and vascular endothelial cells may be the in vivo manifestation of endocytosis of HCV by the LD L receptors that has recently been demonstrated in vitro. The upregula tion of LDL receptors an keratinocytes in inflamed skin is consistent with this postulation.