Cryoglobulinemia

Cryoglobulinemia
Classification and external resources
Specialty
ICD-10	D89.1
ICD-9-CM	273.2
DiseasesDB	3207
MedlinePlus	000540
eMedicine	med/480
Patient UK	Cryoglobulinemia
MeSH	D003449

Cryoglobulinemia or cryoglobulinaemia is a medical condition in which the blood contains large amounts of cryoglobulins – proteins (mostly immunoglobulins themselves) that become insoluble at reduced temperatures. This should be contrasted with cold agglutinins, which cause agglutination of red blood cells. Cryoglobulins typically precipitate at temperatures below normal body temperature (37°C) and will dissolve again if the blood is heated. The precipitated clump can block blood vessels and cause toes and fingers to become gangrenous. Cryoglobulinemia can be associated with various diseases such as multiple myeloma and hepatitis C infection. Cryoglobulins usually consist of IgM directed against the Fc region of IgG.

Classification

Cryoglobulinemia is classically grouped into three types according to the Brouet classification. Type I is most commonly encountered in patients with a plasma cell dyscrasia such as multiple myeloma or Waldenström macroglobulinemia. Types II and III are strongly associated with infection by the hepatitis C virus. Type III is strongly associated with autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis.

There are three different types of cryoglobulins that have been observed to form in the blood.

Type	Composition	Percent	Description
Type I	isolated monoclonal immunoglobulins	10–15% of the total cases	These are composed of a single monoclonal immunoglobulin paraprotein (usually IgM). Sometimes, these are represented by light chains only and can be extracted from the urine (Bence Jones protein); or, they may accumulate in blood serum in the event of renal failure.
Type II	immunocomplexes formed by monoclonal IgM	50–60% of reported cases	They usually have a polyclonal component, usually IgG, and a monoclonal component, usually IgM or IgA, which has an RF function. The IgM can recognize intact IgG or either the Fab region or Fc region of IgG fragments. This is why most type II cryoglobulins are IgM–IgG complexes.
Type III	immunocomplexes formed by polyclonal IgM	25–30% of the reported cases	These have very similar function to the type II cryoglobulins; however, they are composed of polyclonal IgM and IgG molecules.

Types II and III have rheumatoid factor (RF) activity and bind to polyclonal immunoglobulins. These two types are referred to as mixed cryoglobulinemia (MC). When the temperature is raised, the precipitated cryoglobulins will dissolve back into the serum.

In 2006 it was discovered that there are unusual cryoglobulins that show a microheterogeneous composition, with an immunochemical structure that cannot be fit into any of the classifications. A classification of a type II-III variant has been proposed because they are composed of oligoclonal IgMs with traces of polyclonal immunoglobulins

Causes

These proteins may be present in Mycoplasma pneumonia pneumonitis, post streptococcal glomerulonephritis, multiple myeloma, certain leukemias, primary macroglobulinemia, and some autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. This is also found as a symptom in 35% of chronic hepatitis C infections. It can also occur in hepatitis B and human immunodeficiency virus infections. It is important to note that these two different, yet highly representative, clinical syndromes generally reflect different types of underlying CG:

• Hyperviscosity is typically associated with CG due to hematological malignancies and monoclonal immunoglobulins.

• "Meltzer's triad" (purpura, arthralgia and weakness) is generally seen with polyclonal CGs seen in essential, viral, or connective tissue disease-associated CG.

See also

• Cryoglobulinemic purpura
• Hematopoietic ulcer
• Paraproteinemia

External links

• Overview at Mayo Clinic

• DiagnoseMe, Season 1 - episode 6: Cold Blooded...see a case story [1]