Cryoglobulinemia is one of those conditions where the name really says it all—cryo (cold) + globulins (antibodies).

Definition

It’s a disorder where abnormal immunoglobulins (antibodies) precipitate out of serum at cooler temperatures (usually below 37 °C) and then re-dissolve when warmed. These cryoglobulins can deposit in blood vessels, causing Vasculitis (inflammation of small- to medium-sized vessels).

Types (classic Brouet classification)

1. Type I – a single monoclonal immunoglobulin (usually IgM or IgG) → plasma cell disorder
   • MM - Multiple Myeloma (IgM, or IgG), Waldenström’s macroglobulinemia (IgM)
   • Clinical: hyperviscosity, Raynaud’s, thrombosis.
2. Type II – monoclonal IgM (with rheumatoid factor activity) + polyclonal IgG.
   • Most commonly associated with chronic HCV infection → Chronic B cell stimulation
   • Clinical: Vasculitis , arthralgia, neuropathy, MPGN
3. Type III – mixed polyclonal IgM + polyclonal IgG.
   • Associated with SARD (Sjogren’s Disease → Chronic B cell stimulation)
   • Clinical: similar to type II, but usually milder.