Mixed cryoglobulinaemia, when not secondary to other well-defined immunological disorders, is commonly associated with hepatitis C virus (HCV)
infection. However, a minority of cases lack evidence of HCV
infection and are, therefore, defined as 'true essential' mixed cryoglobulinaemias. We thoroughly investigated three such patients to determine the aetiology of this disorder.
Antibodies to HCV (anti-HCV) and HCV
RNA, detected by sensitive
enzyme-linked
immunosorbent and polymerase chain reaction assays in serum and in concentrated
cryoglobulins, were repeatedly negative in the three patients. Despite the lack of evidence for HCV
infection, two of them were still treated with
interferon alpha-2a assuming unrecognized
viral infection. Both patients demonstrated excellent clinical and laboratory responses, but cryoglobulinaemia relapsed after the withdrawal of
therapy. At the time of relapse, HCV
RNA genomic sequences were detected for the first time in the cryoprecipitates of both patients. In the third case, HCV
RNA was demonstrated for the first time during a flare of cryoglobulinaemia coincident with
varicella infection. In all three patients
anti-HCV antibodies remained negative throughout follow-up. We conclude that some apparently 'essential' forms of mixed cryoglobulinaemia can be caused by occult HCV
infection.
Interferon therapy can be taken into consideration in such HCV-negative cases.