title: Relapse of hepatitis C virus-associated mixed cryoglobulinemia vasculitis in patients with sustained viral response.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Université Pierre et Marie Curie-Paris 6, CNRS, UMR 7087, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Dan-Avi
authors.initials: DA
authors.lastname: Landau
authors.forename: David
authors.initials: D
authors.lastname: Saadoun
authors.forename: Philippe
authors.initials: P
authors.lastname: Halfon
authors.forename: Michelle
authors.initials: M
authors.lastname: Martinot-Peignoux
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.forename: Elena
authors.initials: E
authors.lastname: Fois
authors.forename: Patrice
authors.initials: P
authors.lastname: Cacoub
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D003449:Cryoglobulinemia / Q000821:virology*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D016393:Lymphoma, B-Cell / Q000150:complications; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012254:Ribavirin / Q000627:therapeutic use; D014657:Vasculitis / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D012254:Ribavirin