The cryoglobulinaemias

Abstract

Cryoglobulins are immunoglobulins that precipitate in vitro at temperatures less than 37°C and produce organ damage through two main pathways: vascular sludging (hyperviscosity syndrome, mainly in type I cryoglobulinaemia) and immune-mediated mechanisms (principally vasculitis, in mixed cryoglobulinaemia). Cryoglobulinaemia is associated with many illnesses, which can be broadly grouped into infections, autoimmune disorders, and malignancies; the most common cause is infection with hepatitis C virus. Mixed cryoglobulinaemic syndrome is diagnosed when a patient has typical organ involvement (mainly skin, kidney, or peripheral nerve) and circulating cryoglobulins. Cutaneous purpura is the most common manifestation of cryoglobulinaemic vasculitis. The most frequently affected internal organs are the peripheral nerves, kidneys, and joints. The course varies widely and prognosis is influenced by both cryoglobulinaemic damage to vital organs and by comorbidities associated with underlying diseases. More than 90% of cases of cryoglobulinaemia have a known underlying cause; therefore treatment is focused on the cause of the disorder rather than merely symptomatic relief. Studies suggest that both combined or sequential antiviral therapies and targeted biological treatments might be more effective than monotherapy.