Another group of researchers from northern Italy reported on 66 patients with mixed cryoglobulinemia and frank vasculitis, 54 (82%) of whom were positive for HCV. They compared this group with 33 HCV-positive patients who were either cryoglobulin negative or had detectable cryoglobulins but were asymptomatic, and with 48 healthy blood donors. They found a significantly higher frequency of BLyS positivity, both among patients with mixed cryoglobulinemia and among those who were HCV positive without evidence of cryoglobulins.
These investigators also noted that their finding of a subgroup of patients with mixed cryoglobulinemia without HCV infection suggests that other infectious agents also may be capable of triggering the BLyS deregulation that results in the formation of cryoglobulins (Rheumatology 2007;46:37–43).
The need for investigations into other possible etiologic factors also was highlighted in a recent presentation at the International Congress on Autoimmunity in Sorrento, Italy. Dr. Jan Willem Cohen Tervaert reviewed the experience at the University Hospital Maastricht, the Netherlands, where 22 patients with cryoglobulinemia have been treated during the past 5 years—none of whom had HCV detectable either serologically or by polymerase chain reaction. In the Netherlands, the prevalence is low, at 0.098%, with infection found primarily among drug users and immigrants, he said.
In this group of patients, 86% had constitutional symptoms such as fever and malaise. Skin vasculitis and glomerulonephritis each were present in 41%, arthritis in 73%, and peripheral neuropathy in one-third. C-reactive protein was elevated in 73%, RF was present in 67%, and complement levels were low in 70%. Despite the fact that none of the patients had HCV infection, liver function abnormalities were seen in 36%, Dr. Cohen Tervaert said. Two had vasculitis associated with lymphoproliferative disease and 10 also had connective tissue diseases such as Sjögren's syndrome and SLE.
This series demonstrated that non-HCV cryoglobulinemia tends to be more severe than when the autoimmune disorder results from HCV, he said.
This observation also was made by Dr. Cacoub's group in Paris, who compared 65 patients with non-HCV cryoglobulinemia with 118 patients with HCV infection and cryoglobulinemia. The non-HCV patients had a fourfold increased risk of developing B-cell non-Hodgkins lymphoma (Arch. Intern. Med. 2006;166:2101–8).