Type II mixed
cryoglobulinemia (MC) is a
systemic vasculitis, associated in most cases with hepatitis C virus (HCV)
infection, sustained by proliferation of oligoclonal cells. Systemic B cell depletion and clinical remission can be achieved in
non-Hodgkin lymphoma by human/mouse chimeric
monoclonal antibody that specifically reacts with the
CD20 antigen (
rituximab). Similar effects could be expected in type II MC. Twelve patients, mean age 61.9 years (range 37-76), 11 with HCV
infection genotype 2a2c (4 cases) or 1b (6 cases) and 3 (1 case) and symptomatic type II MC with systemic manifestations, including renal involvement, marrow clonal restriction, large necrotizing
ulcers, and
polyneuropathy, were considered eligible for
rituximab therapy because of resistance or intolerance to conventional
therapy or important bone marrow infiltration.
Rituximab was administered intravenously at a dose of 375 mg/m2 on days 1, 8, 15, and 22. Two more doses were administered 1 and 2 months later. No other immunosuppressive drugs were added. Response was evaluated by assessing the changes in clinical signs, symptoms, and laboratory parameters. Levels of
proteinuria,
hematuria, erythrocyte sedimentation rate, cryocrit,
rheumatoid factor, and
IgM decreased while C4 values increased and HCV viral load remained stable during short- and medium-term observation. Bone marrow abnormalities were found to reverse to normal. Constitutional symptoms disappeared or ameliorated. No acute or delayed side effects were seen. Based on this experience and a number of reports published in the last 5 years,
Rituximab appears to be a safe and effective therapeutic option in symptomatic patients with HCV-associated MC with signs of
systemic vasculitis.