Cryoglobulinemia Summary



Cryoglobulins:

 • Cryoglobulins are Igs in the serum that precipitate in vitro at temperatures below 37°C and redissolve on rewarming.

 • They can activate the immune system, leading to the deposit of immune complexes in tissues causing endothelial injury and end-organ damage.

 • They can cause:

	- Arthralgia

	- Purpura

	- Skin ulcers

	- Glomerulonephritis

	- Peripheral neuropathy

 • Cryoglobulins Cause Organ Damage Through 2 Different Pathways:

	- 1. Vascular Sludging (Hyperviscosity Syndrome, Mainly in Type I Cryoglobulinemia)

	- 2. Immune-Mediated Mechanisms (Principally Vasculitis, in Mixed Cryoglobulinemia)



Meltzer's Triad - Mixed Cryoglobulinemia Syndrome:

 • Clinical triad of Palpable purpura, Arthralgia, Weakness.

 • It is generally seen with the mixed cryoglobulinemia syndrome in 80% of patients.



Etiology - Mixed Cryoglobulinemia Syndrome

 • Idiopathic

 • Infections: HCV infection, HBV infection, HIV infection

 • Autoimmune diseases:

	- 10% SLE or RA

	- 5 to 20% Sjögren's syndrome - type II cryoglobulinemia

 • Lymphoproliferative disorders.



Types:

 • Type I Cryoglobulins:

	- Single monoclonal immunoglobulins usually associated with hematological disorders.

 	- (Ischemia, livedo reticularis & skin necrosis, peripheral neuropathy, arthralgia, and arthritis)

 • Types II and III are Mixed Cryoglobulins:

	- Composed of monoclonal or polyclonal IgM respectively, having rheumatoid factor activity that bind to polyclonal immunoglobulins.

 • Type III Often Secondary to Autoimmune Disorders.



Labs/Diagnosis:

 • Cryocrit - Detect the presence of serum cryoglobulins

 • Elevated serum rheumatoid factor level

 • Low serum C4 complement level

 • Immunofixation - Dissolved cryoglobulin

 • Viral serologies

 • Biopsies of organs involved.



DDX:

 • ANCA (Antineutrophil cytoplasmic antibody) associated vasculitis - GPA, EGPA, microscopic polyangiitis.

 • IgA vasculitis (Henoch-Schönlein purpura)

 • Cutaneous small-vessel vasculitis

 • Hypersensitivity vasculitis

 • Vasculitis associated with connective tissue disorder (e.g. systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjögren's syndrome)



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