Cryoglobulinemia

Presence of serum cryoglobulins (single or mixed immunoglobulins that can undergo reversible precipitation at low temperatures)


	Cryofibrinogenemia : cryoprecipitate in plasma made up primarily of fibrinogen; can be primary or secondary to malignancy, autoimmune connective tissue disease or infection; presents with leg ulcers, livedo reticularis or purpura

Types II/III have rheumatoid factor (RF) activity and bind to polyclonal immunoglobulins; immune complexes form from circulating cryoglobulins and are subsequently deposited within blood vessel walls causing vasculitis
Histology: leukocytoclastic vasculitis
Treatment: directed at any underlying disease (i.e. HCV: IFNα + ribavirin)

Type

Immunoglobulins

Underlying Associations

Clinical Findings

Monoclonal IgM or IgG
(no rheumatoid factor activity)

Lymphoproliferative disorders (LPD), plasma cell dyscrasias

Raynaud’s phenomenon, purpura, acrocyanosis, arterial thrombosis

II (Mixed)

Monoclonal IgM (or IgG) with polyclonal IgG

HCV, autoimmune connective tissue diseases, LPD

Vasculitis with palpable purpura, arthralgias, glomerulonephritis, peripheral neuropathy

III (Mixed)

Polyclonal IgM complexed with polyclonal IgG


		IFN treatment worsens peripheral neuropathy