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Cryoglobulines

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Presence of serum proteins that precipitate at <37oC (less than body temperature) and redissolve on rewarming
  • Serum proteins may be IgG, IgM or both
  • Associated with:
    • Multiple myeloma and macroglobulinemia (monoclonal)
    • Hep C, Hep B, SLE, RA, Sjogren syndrome (mixed)
 
Classificação
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  • Type I: monoclonal IG (IgM>>IgG>>IgA)
    • Mechanism: ichemic vasculopathy without vasculitis
    • Associations: Lymphoproliferative disorders (B cell Lymphoma, CLL, NHL)
    • H/E: Ischemic vasculopathy (no vasculitis, no immune complex deposition)
  • Type II (mixed): monoclonal IgM against polyclonal IgG
  • Type III (mixed): polyclonal immunoglobulins (IgG/IgM)
    • Both type II and III
      • Associations
        • Mainly infections caused by “slow” virus (HCV)
        • Connective tissue diseases (Sjogren)
        • Lymphoproliferative disorders
      • H/E: leukocytoclastic vasculitis
 
Apresentação clínica
  • Type 1 → ichemic vasculopathy without vasculitis
    • Raynaud phenomenon
    • Livedo reticularis → racemosa → non-inflammatory retiform purpura
    • Gangrene
    • Acrocyanosis
  • Type 2 and 3 → small and medium vessel vasculitis
    • Small
    • Medium
        • Mostly systemic, main visceral arteries
          • renal - renal artery aneurysm, renovascular hypertension
          • hepatic
          • coronary
          • mesenteric
        • Skin
          • Reticular dermis vessels affected
          • Paniculitis (→ subcutaneous nodules)
          • livedo (livedo reticularis, racemosa, inflammatory retiform purpura)
          • ulcers
          • digital necrosis
          • But not palpable purpura
  • Crops occur spontaneously from cold exposure or prolonged sitting or standing
  • Last 3-10 days
  • Overlap
    • Palpable purpura
    • Livedo reticularis, urticaria, digital ulceration and gangrene can occur
    • Because mixed ischemic vasculopathy with leukocytoclastic vasculitis
 
Exames complementares
  • +RF (not in type I) or ANA; 20% with anti-SM, anti-Ro, Anti-La
  • Test for circulating cryoglobulines
    • Collection tubes prewarmed to 37ºC without anticoagulants
    • Sample kept at 37ºC
    • May have false negatives
 
Tratamento
  • Treatment of HCV or hematologic disorder
  • Avoid cold
  • Plasmapheresis, steroids, IVIg, Azathioprine