12- CRYOGLOBULINEMIA

• Cryoglobulins


  Immunoglobulins (Igs) in the serum that precipitate at temperatures below 37°C and re-dissolve on rewarming
• Cryoglobulinemia


  The presence of cryoglobulin in a patient's serum
• Cryoglobulinemia


  • Systemic inflammatory syndrome that involves small-to-medium vessel vasculitis due to cryoglobulin-containing immune complexes
• Essential cryoglobulinemia


  Not associated with other diseases
• Secondary cryoglobulinemia


  Associated with other diseases
• Types of cryoglobulinemia


  • Type I
  • Type II
  • Type III
• Type I cryoglobulinemia


  • Cryoglobulins are monoclonal IgM or IgG
  • Associated with waldenstroms and multiple myeloma
• Type II cryoglobulinemia


  • Also known as "mixed cryoglobulinemia"
  • Has 2 components: monoclonal cryoglobulins - IgM, polyclonal cryoglobulins - IgG (4 subtypes: IgG1, IgG2, IgG3, IgG4)
  • Commonly seen in hepatitis C patients
  • May also be associated with HBV, HIV, SLE, Sjögren's syndrome, and lymphoproliferative disorders (NHL)
• Type III cryoglobulinemia


  • Mixture of polyclonal IgG (all isotypes) and polyclonal IgM
  • Often secondary to autoimmune disorders
• Clinical features of cryoglobulinemia

  • Isolated proteinuria or hematuria
  • RPGN
  • Constitutional symptoms: Fever, fatigue, fibromyalgia
  • Articular: arthralgia & arthritis
  • Vascular: purpuric skin rash, Raynaud's, digital infarct, necrotizing vasculitis
  • Neurological: peripheral neuropathy (especially mononeuritis multiplex presenting with sudden wrist/foot drop due to vascular infarct of the nerve), CNS involvement
• Diagnosis of cryoglobulinemia


  • Suspected from clinical features and history of a secondary cause
  • Lab hallmark: measurable amount of cryoglobulin (cryocrit) with a low C4 complement level
  • Renal biopsy would show a steak-like beefy glomerulus
• Management of cryoglobulinemia


  1. Treat underlying disease (hepatitis C, Sjogren syndrome, etc.)

  2. Plasma exchange (if have vasculitic lesions or mononeuritis multiplex)

  3. Immunosuppression (steroid + cyclophosphamide)