Relapse of hepatitis C virus-associated mixed cryoglobulinemia vasculitis in patients with sustained viral response

Arthritis Rheum. 2008 Feb;58(2):604-11. doi: 10.1002/art.23305.


Objective: To investigate the clinical characteristics, outcomes, and results of hepatitis C virus (HCV) RNA analyses in a group of patients with HCV-associated mixed cryoglobulinemia (MC) vasculitis who experienced a relapse of vasculitis despite achieving a sustained viral response to treatment with antiviral agents.

Methods: HCV RNA testing was performed by the transcription-mediated amplification (TMA) method in sera and cryoprecipitates (detection limit 2.5 IU/ml). HCV replication was assessed in peripheral blood mononuclear cells (PBMCs) by a modified real-time polymerase chain reaction assay (detection limit 15 IU/10(6) cells).

Results: We identified 8 patients with relapse of HCV-MC vasculitis despite their having achieved a sustained viral response to treatment. Relapse appeared early after the end of treatment (mean +/- SD 2.5 +/- 3.5 months) and included mainly purpura (n = 7) and arthralgia (n = 5). Relapse was associated with an increase in serum cryoglobulin levels as compared with end-of-treatment levels (mean +/- SD 0.3 +/- 0.09 gm/liter and 0.08 +/- 0.04 gm/liter, respectively; P < 0.01) and a decrease in C4 levels. In most patients, the relapse was brief, and the MC vasculitis manifestations subsided. A search for HCV RNA by TMA was negative in all patients tested (7 of 8 patients), both in sera and in cryoprecipitates. HCV replication was not found in PBMCs from any of the patients tested (6 of 8 patients). In 3 patients, the MC vasculitis symptoms persisted and were associated with elevated cryoglobulin levels. B cell lymphoma was diagnosed in 2 of these 3 patients.

Conclusion: Relapse of MC vasculitis does occur in a few patients with HCV infection, despite achieving a sustained viral response, and this relapse is not related to persistence of virus. Relapse is short-lived and may be induced by the withdrawal of interferon alfa therapy. However, in patients with persistent MC vasculitis symptoms, a different underlying condition should be considered, especially B cell lymphoma.

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use
  • Cryoglobulinemia / virology*
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Hepacivirus / drug effects
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / drug therapy
  • Humans
  • Interferon-alpha / therapeutic use
  • Lymphoma, B-Cell / complications
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • Recurrence
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribavirin / therapeutic use
  • Vasculitis / virology*
  • Virus Replication / drug effects


  • Antiviral Agents
  • Interferon-alpha
  • RNA, Viral
  • Ribavirin