Medicine & USMLE

Mixed Cryoglobulinemia

  1. Giant Cell (Temporal) Arteritis
  2. Henoch-Schonlein Purpura
  3. Takayasu Arteritis
  4. Buerger Disease (Thromboangiitis Obliterans)
  5. Behcet Disease
  6. Granulomatosis with Polyangiitis
  7. Mixed Cryoglobulinemia
  8. Microscopic Polyangiitis
  9. Kawasaki Disease


Mixed Cryoglobulinemia is a small vessel vasculitis characterized by the presence of cryoglobulins in the blood. These are autoantibodies that bind to Hepatitis C antibodies, resulting in immune complex formation. The immune complexes precipitate at low temperatures, which is where “cryoglobulins” get their name. Since the disease is caused by accumulated immune complexes, it is therefore an example of a type III hypersensitivity reaction. Clinical manifestations include the classic triad of palpable purpura, weakness, and arthralgias. It may also lead to glomerulonephritis and peripheral neuropathy.

Key Points

  • Mixed Cryoglobulinemia
    • Small vessel vasculitis
    • Pathophysiology
      • Occurs secondary to viral infections, especially Hepatitis C
        • More specifically, autoimmune IgM forms against anti-Hep C IgG
          • These are known as cryoglobulins, since they clump together and precipitate at low temperatures
            • Immune complex deposition = type III hypersensitivity reaction
          • Complement activation may lead to low C4 levels
    • Clinical Findings
      • Meltzer’s Triad
        • Palpable purpura
          • Because this is a small vessel vasculitis, small cutaneous vessels are involved
        • Weakness (non-specific)
        • Arthralgias (non-specific)
      • Peripheral neuropathy
      • Glomerulonephritis
        • Secondary to immune complex deposition