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The capillaries are plugged with eosinophilic material, which are precipitated immunoglobulins.

Three types of cryoglobulemia are found. Type 2 and 3 are considered "mixed cryoglobulinemia".


Cryoglobulinemia literally means "cold proteins in the blood". Basically, these immunoglobulins become insoluble below body temperature (~37 degrees celsius) and precipitate in the blood. There are three types of cryoglobulinemia based on the type of immunoglobulin and the presence of rheumatoid factor.

Type I is composed IgM, does not have rheumatoid factor activity and is most commonly associated with multiple myeloma, lymphoma and Waldenstrom macroglobulinemia. Usually, these patients remain asymptomatic until the levels of cryoglobulins cause hyperviscosity syndrome.

Both Type II and type III have rheumatoid factor, which is IgM that binds to the Fc portion of IgG. It can be monoclonal IgM to polyclonal IgG (type II) or polyclonal IgG to polyclonal IgG (type III). Thus, type II and type III are called "mixed cryoglobulinemias". There is a stronge association of types II and III with hep C infection. Other associations include connective tissue diseases and lymphoproliferative disorders (hematologic malignancies).

In type I CG skin biopsies, there may be occlusive, PAS-positive, eosinophilic material within the vessel lumina, representing precipitated immunoglobulin. In types II and III CG, an additional inflammatory component may be present, consisting of vessels infiltrated by neutrophils and occasional eosinophilis and lymphocytes. There may be RBC extravasation and nuclear dust (leukocytoclasia).


A small percentage (between 2% and 15%) of cryoglobulin (+) individuals develop cryoglobulinaemic vasculitis. Clinically, cryoglobulinemic vasculitis may present "Meltzer's triad" of palpable purpura, arthralgia and myalgia.


Treatment varies by patient and may include etiologic (antiviral), pathogenetic (cyclophosfamide, rituximab), or symptomatic (steroids, plasmapheresis) regiments. .


→There are 3 types of cryoglobulinemia. Type I is associated with multiple myeloma. Types II and III are strongly associated with hepatitis C infection.

→Histologically, the vessels in the dermis may be filled with hyaline material. Leukcytoclastic vasculitis is seen more in types II and III whereas inflammation is usually minimal in type I CG.


Busam KJ. Dermatopathology: Foundations in Diagnostic Pathology 1st Ed. Philadelphia, PA: Elsevier; 2010: 199. at - Last accessed on July 4th, 2011.

Last updated: 2012-01-09
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