Long-term effects of anti-CD20 monoclonal antibody treatment of cryoglobulinaemic glomerulonephritis.

BACKGROUND: Type II mixed cryoglobulinaemia (MC) is a systemic vasculitis, associated in most cases with hepatitis C virus (HCV) infection, and sustained by proliferation of oligoclonal cells. Systemic B-cell depletion and clinical remission can be achieved in non-Hodgkin lymphoma by a human/mouse chimeric monoclonal antibody that specifically reacts with the CD20 antigen (Rituximab). Similar effects could be expected in type II MC. METHODS: Six patients, mean age 64.2 years (range: 37-76 years), with HCV infection genotype 2a2c (three cases) or 1b (three cases) and symptomatic type-II MC with systemic manifestations, including renal involvement (five cases) and bone marrow clonal restriction (three cases), were considered eligible for Rituximab therapy. Rituximab was administered intravenously at a dose of 375 mg/m(2) 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 for < or = 18 months. RESULTS: Levels of proteinuria, erythrocyte sedimentation rate and cryocrit significantly decreased at 2, 6 and 12 months. Rheumatoid factor and IgM significantly decreased at 6 months whereas C4 values significantly increased at 2 and 6 months. HCV viral load and immunoglobulin G remained stable. Bone marrow abnormalities were found to reverse to normal in all three positive cases. Constitutional symptoms (skin ulcers, purpura, arthralgia, weakness, paraesthesia and fever) disappeared or improved. No acute or delayed side effects were observed. CONCLUSIONS: Rituximab appears to be a safe and effective therapeutic option in symptomatic patients with HCV-associated MC glomerulonephritis and signs of systemic vasculitis.

Nail fold videocapillaroscopy in mixed cryoglobulinaemia.

BACKGROUND: Nail fold videocapillaroscopy (NVC) has been extensively used to examine morphological and functional changes of microcirculation in connective tissue diseases. The nutritional circulation that depends on tissue capillaries, can be expected to be significantly impacted in mixed cryoglobulinaemia (MC). METHODS: Using NVC, we evaluated 29 patients with MC (19 women), mean age 66 years (range 40-83). They included 28 hepatitis C virus (HCV) positive patients-14 genotype 1b, 10 genotype 2a 2c, two genotype 4, two with undetermined genotype. Of them, 18 had type II (IgMk-IgG) MC and 11 had type III. All patients were symptomatic, presenting with weakness (24 of 29 patients), arthralgia (24), purpura (16), peripheral neuropathy (20), Raynaud's phenomenon (8), hypertension (19) and membranoproliferative glomerulonephritis (MPGN) (9). The nail fold capillaries of four fingers per hand were examined using a videomicroscope. RESULTS: Of the 29 patients, 27 had morphological abnormalities (including tortuosity and apical enlargement), 18 had capillaries with deeply altered orientations, 17 had shortened capillaries and 20 neoangiogenetic phenomena. These four types of capillary abnormalities were simultaneously present in 10, suggesting this combination to be a characteristic pattern in MC. Less common alterations included haemorrhages (10 cases), enlarged and giant capillaries (2) and avascular areas (2). The patients with MC-associated MPGN had a significantly greater number of capillary abnormalities (mean 4.5, range 4-6) than non-nephritic patients (mean 3.5, range 1-6, P = 0.01). The number of capillary abnormalities was not related to the presence of Raynaud's phenomenon. Microcirculatory changes did not correlate with other clinical manifestations or serological indices, including cryocrit, cryoglobulin type, HCV genotype, viral load, haemoglobin, ALT, rheumatoid factor, IgM and C4 levels. CONCLUSIONS: Patients with MC show a variety of microcirculatory changes, often clustered in a characteristic pattern of abnormally oriented, short capillaries and neoangiogenetic phenomena. Capillary changes are more numerous in nephritic patients.