Increased risks of lymphoma and death among patients with non-hepatitis C virus-related mixed cryoglobulinemia

Arch Intern Med. 2006 Oct 23;166(19):2101-8. doi: 10.1001/archinte.166.19.2101.


Background: Data on essential mixed cryoglobulinemia (MC) are scarce, and most date back to studies before 1989 (ie, before the discovery of hepatitis C virus [HCV] infection). Our objective was to describe the spectrum of MC in the era of HCV infection.

Methods: Retrospective study from a single university hospital's database of 1434 patients who tested positive for MC between January 1989 and December 2003.

Results: One hundred thirty-three patients (9%) with persistent MC without HCV were included in the study. Sixty-five of 133 patients who fulfilled the criteria for MC vasculitis were compared with 118 patients with HCV-related MC vasculitis. The patients without HCV had increased frequencies of renal involvement and B-cell non-Hodgkin lymphoma (NHL), lower gammaglobulin levels, and higher death rates. Twenty-three of the patients had B-cell NHL (primarily of the lymphoplasmocytic and marginal zone types), and 8 patients had Sjögren syndrome. In multivariate analysis, a cryoglobulin level higher than 0.6 g/L (odds ratio [OR], 1.44) and the presence of MC vasculitis (OR, 4.3) and hypogammaglobulinemia (OR, 6.7) were independently associated with B-cell NHL. After a mean follow-up of 49.4 months, 18 (14%) of 133 patients had died, primarily of sepsis. In multivariate analysis, age at diagnosis older than 60 years (OR, 1.06) and renal involvement (OR, 5.20) were independently associated with death.

Conclusion: Patients with non-HCV-related MC vasculitis have a poor outcome and have a 4-fold increased risk of developing B-cell NHL.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cryoglobulinemia / complications*
  • Cryoglobulinemia / mortality*
  • Female
  • Hepatitis C / complications
  • Hepatitis C Antibodies / blood
  • Humans
  • Lymphoma, B-Cell / etiology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Retrospective Studies
  • Risk Factors


  • Hepatitis C Antibodies