HCV-unrelated cryoglobulinaemic vasculitis: the results of a prospective observational study by the Italian Group for the Study of Cryoglobulinaemias (GISC)

Clin Exp Rheumatol. 2017 Mar-Apr;35 Suppl 103(1):67-76. Epub 2017 Apr 19.


Objectives: To investigate the clinical and laboratory patterns of HCV-unrelated cryoglobulinaemic vasculitis (CV), and the factors influencing its outcome.

Methods: Prospective study of all anti-HCV and HCV-RNA negative patients with CV who have been observed since January 2004 in 17 centres participating in the Italian Group for the Study of Cryoglobulinaemias (GISC).

Results: 175 enrolled were followed up for 677 person-years. The associated conditions were primary Sjögren's syndrome (21.1%), SLE (10.9%), other autoimmune disorders (10.9%), lymphoproliferative diseases (6.8%), solid tumours (2.3%) and HBsAg positivity (8.6%), whereas 69 patients (39.4%) had essential CV. There were significant differences in age (p<0.001), gender (p=0.002), the presence of purpura (p=0.005), arthralgia (p=0.009), liver abnormalities (p<0.001), sicca syndrome (p<0.001), lymphadenopathy (p=0.003), splenomegaly (p=0.002), and rheumatoid factor titres (p<0.001) among these groups. Type II mixed cryoglobulins were present in 96 cases (54.9%) and were independently associated with purpura and fatigue (odds ratio [OR]4.3; 95% confidence interval [CI] 1.8-10.2; p=0.001; and OR2.8; 95%CI 1.3-6.3; p=0.012). Thirty-one patients died during follow-up, a mortality rate of 46/1000 person-years. Older age (for each additional year, adjusted hazard ratio [aHR] 1.13; 95%CI 1.06-1.20; p<0.001), male gender (aHR 3.45; 95%CI 1.27-9.40; p=0.015), type II MCG (aHR 3.31; 95%CI 0.09-1.38; p=0.047) and HBsAg positivity (aHR 7.84; 95%CI 1.20-36.04; p=0.008) were independently associated with greater mortality.

Conclusions: HCV-unrelated CV is a multifaceted and often disabling disorder. The associated conditions influence its clinical severity, giving rise to significantly different clinical and laboratory profiles and outcomes.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Biomarkers / blood
  • Complement System Proteins / metabolism
  • Cryoglobulinemia / blood
  • Cryoglobulinemia / epidemiology*
  • Cryoglobulinemia / immunology
  • Cryoglobulinemia / mortality
  • Cryoglobulins / metabolism
  • Disease Progression
  • Female
  • Humans
  • Incidence
  • Inflammation Mediators / blood
  • Italy / epidemiology
  • Kaplan-Meier Estimate
  • Logistic Models
  • Male
  • Multivariate Analysis
  • Odds Ratio
  • Prevalence
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Severity of Illness Index
  • Systemic Vasculitis / blood
  • Systemic Vasculitis / epidemiology*
  • Systemic Vasculitis / immunology
  • Systemic Vasculitis / mortality
  • Time Factors


  • Biomarkers
  • Cryoglobulins
  • Inflammation Mediators
  • Complement System Proteins