Mixed cryoglobulinemia

Mixed cryoglobulinemia (MC) includes:MC type II, composed by polyclonal IgGmonoclonal IgM, and MC type III, composed by polyclonal IgG-polyclonal IgM immune-complexes. MC may be secondary to various immunological,hematological, and infectiousd iseases, or it can represent a distinct disorder, the ‘essential’ MC. Following the discovery of a causative role of HCV, the term ‘essential’ is now referred to only a small percentage of patients. MC classification criteria include: serum mixed cryoglobulins, hypocomplementemia (low C4), leukocytoclastic vasculitis, typical clinical triad - purpura, weakness, arthralgias-, and multiple organ involvement.MC may share various clinico-serological features with different immunological/ neoplastic diseases; differential diagnosis should take in account other systemic vasculitides, Sjogren’s syndrome, autoimmune hepatitis, and B-cell lymphomas. MC syndrome is an immune-complex mediated systemic vasculitis (leukocytoclastic vasculitis) involving the small vessels, clinically characterized by cutaneous manifestations (orthostatic purpura, and ulcers), liver, renal, peripheral nerves, widespread vasculitis, and possible development of neoplastic disorders, mainly B-cell lymphomas.MC cumulative survival is significantly lower if compared to general population.Treatment of MC syndrome is particularly challenging because of its complex etiopathogenesis, including HCV infection, autoimmune, and lymphoproliferative alterations; it may include etiological, pathogenetic, and/or symptomatic therapies. An attempt to eradicate the HCV (interferon ribavirin) should be done in all HCV-related MC, particularly in those with active hepatitis. The immunosuppressors (cyclophosphamide or rituximab), alone or in combination with high dosage steroids and/or plasma exchange, can be usefully employed in MC patients with severe/active complications (glomerulonephritis, widespread vasculitis, sensory-motor neuropathy).