Background/Purpose: Mixed cryoglobulinemia syndrome (MCs) is a systemic vasculitis
characterized by multiple organ involvement due to the vascular deposition of
IgMk/IgG cryoglobulins. B cells expansion usually triggered by HCV infection
plays a central role in MCs.
Objectives: to evaluate the long term effects of B-cells depletion in MCs
Methods: Twenty seven patients, (mean age 60.2 [range 35-78] years,
HCV infection in 96% of cases) with symptomatic type-II MCs with systemic
manifestations, including renal involvement (diffuse membranoproliferative
glomerulonephritis in 15 cases), peripheral neuropathy (26 cases) and large
skin ulcers (9 case, in 7 necrotizing) were considered eligible for Rituximab
(RTX) therapy. RTX was administered 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, laboratory parameters and
electromyographic indices for a very long term follow-up (mean 54.3 months
[12-96])
Results: Complete remission of pre-treatment active manifestations was
observed in all the cases of skin purpuric lesions and non-healing vasculitic leg
ulcers, and in 80% of cases of peripheral neuropathy. A significant improvement
in the clinical neuropathy disability score was observed. Electromyography
revealed that the amplitude of compound motor action potential had increased.
Cryoglobulinemic glomerulonephritis, observed in 15 patients, significantly
improved during the follow-up starting from the second month after RTX (serum
creatinine from 2.2±1.9SD to 1.6±1.2SD mg/dl, p≤.05; 24-hour proteinuria from
2.3±2.1SD to 0.9±1.9SD g/24h, p≤.05). Significant improvement of serological
hallmarks, such as cryocrit and low complement C4, were also detected
(p≤.05). The safety of RTX was confirmed by the absence of side effects
recorded during the mean 54-month follow-up. Re-induction was performed in
9 relapsed cases (after a mean of 31.1 months, range 12-54) with resolutive
beneficial effects.
Conclusion: In this open prospective study, the “4 plus 2 infusion protocol”
of RTX appeared to be very effective and safe in the treatment of patients with
MCs-associated membranoproliferative nephritis, polyneuropathy and severe
skin involvement

ACR Meeting Abstracts - https://acrabstracts.org/abstract/very-long-term-effects-of-the-4-plus2-infusion-protocol-of-rituximabalone-in-patients-with-hcv-associatedmixed-cryoglobulinemia-with-diffusemembranoproliferative-glomerulonephritiss/