23rd July 2024

Cryoglobulinaemia

Cryoglobulins are Igs that precipitate out at temperatures below 37°C. Cryoglobulinaemia refers to the presence of cryoglobulins in serum.

There are three types:

• Type I: monoclonal Ig production (usually IgM, sometimes IgG). Associated with monoclonal gammopathies.
• Type II: mixed cryoglobulinaemia; monoclonal Ig (usually IgM) forms a complex with polyclonal Igs (usually IgG). Associated with chronic viral infections, especially hepatitis C, autoimmune disorders and lymphoproliferative disorders.
• Type III: mixed cryoglobulinaemia; polyclonal IgM forms a complex with polyclonal IgG. Associated with autoimmune conditions and sometimes chronic viral infections, mainly hepatitis C.

Type I presents with hyperviscosity syndrome and signs of small vessel obstruction (e.g. acrocyanosis, digital ischaemia, skin necrosis).

Mixed cryoglobulinaemia often presents with Meltzer’s triad of purpura, arthralgia and weakness. It can also cause glomerulonephritis and peripheral neuropathy.

Diagnosis is by identification of cryoglobulins in the blood with investigation for underlying precipitants.

Treatment requires management of any underlying conditions. Symptomatic mixed cryoglobulinaemia may be treated with steroids ± cyclophosphamide, depending on severity. Hyperviscosity syndrome requires urgent plasmapheresis.