| 
 two categories: 
| • | type I – a single monoclonal immunoglobulin |  
 | • | type II (mixed) – more than one class of immunoglobulin, usually IgM and IgG with the IgM having rheumatoid factor activity directed against IgG molecules  (classified as either “essential” meaning idiopathic;  or "secondary" to CTD or infection) |  
 Monoclonal CRYOGLOBULINEMIA 
| • | are essentially monoclonal proteins with abnormal thermal behavior  |  
 | • | usually detected in patients with plasma cell malignancies (e.g. multiple myeloma, CLL, Waldenstrom’s macroglobulinemia) |  
 | • | histology = amorphous eosinophilic material in the vessel lumen (=intravascular deposits of cryoglobulins) (no LCV) |  
 mixed CRYOGLOBULINEMIA 
| • | represent cold-precipitable immune complexes (reflecting the fact that low temperatures increase the stability of Ag-Ab interactions and enhance precipitation) |  
 | • | in patients with autoimmune disease (e.g. RA, SLE, Sjögren’s) or chronic infection (especially Hepatitis C) |  
 | • | the most frequent type of mixed cryoglobulin is IgM-IgG, in which IgM is a “rheumatoid factor” |  
   
Essential mixed cryoglobulinemia: 
| • | = there is no detectable autoimmune, lymphoproliferative, or infectious disease present  |  
 | • | characterized by chronic course with intermittent palpable purpura, polyarthralgia, Raynaud’s, and occasionally glomerulonephritis. |  
   
| • | it is believed that, at least in some cases, the IgM antibody is directed to determinants expressed by IgG antibodies bound to an antigen (e.g. an unknown viral antigen) |  
 | • | it is believed that this mechanism, anti-viral IgG combined with an IgM anti-antibody, accounts for over 50% of the cases of essential or idiopathic cryoglobulinemia  |  
  | 
 
 
 
  
| • | blood is drawn and clotted at 37ºC, serum is immediately separated, without cooling, and immediately after centrifugation, 5-10ml of serum are placed in a refrigerator at 4-8°C |  
 | • | the serum will be examined daily, up to 72 hours for appearance of a precipitate (i.e. cryos) |  
  | 
 
 
 
  
clinical ddx:  can look Schamberg's-like (Cayenne-pepper) vs. Waldenstrom's hyperglobulinemic purpura (Cayenne pepper) 
(cryos can look like BPP with small ulcers) 
  
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