Cryoglobulinemia: The Basics, and Two Revelations

Cacoub P, Comarmond C, Domont F, et al. Cryoglobulinemia Vasculitis. American Journal of Medicine. 2015; doi: 10.1016/j.amjmed.2015.02.017. Online: March 30, 2015.

Michaud M, Moulis G, Puissant B, et al. Cryofibrinogenemia: a marker of severity of cryoglobulinemia vasculitis.American Journal of Medicine. 2015; doi: 10.1016/j.amjmed.2015.03.009. Online: March 28, 2015.

Cryoglobulinemic vasculitis is a small vessel disease, usually caused by hepatitis C virus (HCV), but may appear with an underlying autoimmune or hematologic disorder. A review by clinicians from France (the first article above) describes the types of cryoglobulinemic vasculitis and discusses treatment options.

The disease generally involves the skin, joints, peripheral nervous system, and kidneys.  The main types are:

•   Type I: A B-cell lymphoproliferative disorder with a single monoclonal immunoglobulin and a 10-year survival of 87%.

•   Type II and III: Polyclonal IgG, with or without monoclonal IgM with rheumatoid factor activity, and a 10-year survival of 65% (often called mixed cryoglobulinemia).

In HCV-negative disease, there is a higher risk of death for patients over the age of 65 who have pulmonary, gastrointestinal, and renal involvement.

In HCV-positivedisease:

•   good outcomes are possible with antivirals but not with immunosuppressants;

•   for patients with severe vasculitis, rituximab with or without plasmapheresis is required before initiation of antiviral therapy, according to these authors.

Both HCV-positive and HCV-negative patients face an increased risk of lymphoma.

The second article, also by authors from France, reports a finding of detectable cryofibrinogen (CF) in 18 of 29 patients with cryoglobulinemia. CF is linked with a more severe phenotype, according to the authors.

They also note that cancers and hematological disorders are more frequent among CF-positive patients.

Other key findings from their retrospective study: Patients who have higher levels of alpha-1 and alpha-2 globulinemia are more likely to have cryoglobulinemia vasculitis, and are more likely to use corticosteroids, immunosuppressants, or plasmapheresis.