Hepatitis C Virus-associated Cryoglobulinemic Livedo Reticularis Improved with Direct-acting Antivirals

Abstract

We herein report a case of hepatitis C virus (HCV)-associated cryoglobulinemic livedo reticularis in a woman in her 60s that improved with direct-acting antivirals (DAAs). Hyperpigmentation was observed in both lower legs, and a skin biopsy confirmed livedo reticularis, suggesting a relationship with cryoglobulinemia and HCV infection. DAAs with an NS5A inhibitor+NS3/4A protease inhibitor (glecaprevir/pibrentasvir) were administered for eight weeks, and a sustained virological response (SVR) was obtained. The disappearance of serum cryoglobulin was confirmed approximately two years after an SVR was obtained and livedo reticularis was improved. DAA therapy can be an effective therapeutic option for extrahepatic complications associated with HCV infection.

Keywords: cryoglobulin; direct-acting antivirals (DAAs); hepatitis C virus; livedo reticularis.

Figure 1.

Imaging findings of the lower legs before DAA treatment. Macular and papular purpura and brown pigmentation were observed on both lower legs. (a) Front imaging. (b) Front close-up imaging. (c) Back imaging.

Figure 2.

Histopathology of livedo reticularis of the lower legs. (a) Hematoxylin and Eosin staining, low-magnified imaging. (b) High-magnified histopathological imaging of the upper dermis. Yellow-brown hemosiderin deposits are observed in the upper dermis (arrows), and erythrocyte leakage and nuclear fragments are also observed around the blood vessels (arrowheads). (c) High-magnified histopathological imaging of subcutaneous adipose tissue. Fibroblasts with collagen fibers, fibrous tissue with mast cells, and angiogenesis were observed throughout adipose tissue. In addition, fibrin clumps can be seen, showing recanalization of the blood vessels occluded by vasculitis (arrows).

Figure 3.

The treatment course of this patient. The patient was started on an eight-week direct-acting antiviral (DAA) regimen of an NS5A inhibitor+NS3/4A protease inhibitor (glecaprevir/pibrentasvir; Mavillet^®). HCV RNA disappeared in the second week of administration, and a sustained virological response (SVR) at 24 weeks (SVR24) was obtained. Approximately two years after achieving SVR24, serum cryoglobulins disappeared, and the lower legs showed a clear improvement in the mottled, papular purpura and brown pigmentation.

Figure 4.

Imaging findings of the lower legs two years after achieving SVR24. There was an improvement in the purpura on both lower legs. (a) Front imaging. (b) Front close-up imaging. (c) Back imaging.