Mixed cryoglobulinemia (MC) is a systemic vasculitis secondary to circulating immune
complex deposition in the small vessels. In the overwhelming majority of patients,
hepatitis C virus (HCV) infection represents the triggering factor of the disease.
MC is characterized by multiple organ involvement, mainly skin, liver, renal, peripheral
nerves, and less frequently by widespread vasculitis and cancer.
To investigate the demographic, clinical, serologic features, and survival in a large
series of MC patients.
The study included 231 MC patients recruited between 1972 and 2001 at the Rheumatology
Unit of the University of Pisa. All patients underwent wide clinicoserologic and virologic
assessment. Cumulative survival rates were computed by the Kaplan-Meier method; moreover,
the prognostic relevance of the main variables was investigated by Cox model analysis.
In 92% of cases, the presence of HCV infection was demonstrated (anti-HCV antibody,
92%; HCV RNA, 90%), whereas hepatitis B virus (HBV) represented the possible causative
agent in only 1.8% of patients (HBV DNA). Clinically, the MC syndrome followed a relatively
benign clinical course in over 50% of cases, whereas a moderate-severe clinical course
was observed in one third of patients whose prognosis was severely affected by renal
and/or liver failure. In a limited, but significant, percentage (15%) of individuals,
the disease was complicated by a malignancy, ie, B-cell lymphoma, and less frequently
by hepatocellular carcinoma, or thyroid cancer. The survival study by the Kaplan-Meier
method revealed a significantly lower cumulative 10th-year survival, calculated from
time of diagnosis, in MC patients compared with expected death in the age- and sex-matched
general population. Moreover, significantly lower survival rates were observed in
males and in subjects with renal involvement. The multivariate analysis by the Cox
proportional hazard regression model further supported the above findings: an increased
mortality risk of 98% was observed for male gender (male/female hazard ratio, 1.978)
and of 197% in patients with, compared with those without, renal involvement (hazard
ratio, 2.967). At the end of the follow-up, 97 patients were deceased, and in 79 of
97 patients, the causes of death were ascertained: nephropathy (33%), malignancies
(23%), liver involvement (13%), and diffuse vasculitis (13%) were the most frequent
causes of death.
Careful patient monitoring is recommended for a timely diagnosis of life-threatening
MC complications, mainly nephropathy, widespread vasculitis, and B-cell lymphoma or
other malignancies.