Cryoglobulin: immunoglobulins (Ig) + complement components = precipitate,  upon refrigeration of serum

 

cryoglobulinemia syndromen:

vasculitis: small to medium vessel vasculitis door CG-containing immune complexes

hyperviscosity (due to hematological malignancies and monoclonal Ig)

"Meltzer's triad": palpable purpura, arthralgia, and myalgia; generally with polyclonal CGs

 

Classificatie: idiopathic or secondary, en

 

Brouet:

Type I CG (5 to 25 percent of CG)

isolated monoclonal Ig (typically IgG or IgM) is present

usually associated with a hematologic malignancy such as WM or MM

often asymptomatic

hyperviscosity and/or thrombosis

Raynaud phenomenon, digital ischemia, livedo reticularis, purpura, and neurology

involves: skin, kidney, and bone marrow

 

MIXED

Type II CG (40 to 60 percent of CG)

- mixture of polyclonal Ig with monoclonal Ig, typically IgM or IgA, with RF activity

- often due to persistent viral infections, particularly HCV and HIV

type III CGs (40 to 50 percent of CG)

- polyclonal Ig characterizes

- systemic rheumatic diseases

involves skin, peripheral nervous system, and kidney

autopsy studies: extensive / often clinically inapparent, vasculitis in additional sites

constitutional and nonspecific symptoms, such as arthralgias, fatigue, and myalgias

palpable purpura due to cutaneous vasculitis and sensory changes or weakness due to peripheral neuropathy

pulmonary manifestations, often subclinical, may occur

immune complex renal disease

 

Minute levels sometimes detectable in healthy persons: ongoing physiological clearance of endogenous immune complexes by Ig with RF activity

 

Pathogenic CG responses:

- chronic immune stimulation and/or lymphoproliferation: higher concentrations of mono-, oligo-, or polyclonal CG

- immune complex formation among CG and/or their target antigens

- defective and/or insufficient clearance of the resulting immune complexes

 

majority asymptomatic, generally correlated with the underlying CG type

 

LAB/ decreased levels of complement, elevated acute phase reactants, autoantibodies, and positive viral serologies

 

no significant morbidity or mortality risk over and above the underlying conditions

wel: renal failure and development of a lymphoproliferative or plasma cell disorder.