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Cryoglobulinemia

Immunoglobulins which undergo reversible precipitation at 4 deg C, dissolve when warmed to 37 deg C. One-third of cases are idiopathic

Three types

  • type I (25%):
    • monoclonal - IgG or IgM
    • associations: multiple myeloma, Waldenstrom macroglobulinaemia
  • type II (25%)
    • mixed monoclonal and polyclonal: usually with rheumatoid factor
    • associations: hepatitis C, rheumatoid arthritis, Sjogren's, lymphoma
  • type III (50%)
    • polyclonal: usually with rheumatoid factor
    • associations: rheumatoid arthritis, Sjogren's

Possible features

  • Raynaud's only seen in type I
  • cutaneous
    • vascular purpura
    • distal ulceration
    • ulceration
  • arthralgia
  • renal involvement
    • diffuse glomerulonephritis

Investigations

  • low complement (esp. C4)
  • high ESR

Management

  • treatment of underlying condition e.g. hepatitis C
  • immunosuppression
  • plasmapheresis

Questions

  1. A 68-year-old woman is referred to the rheumatology department with Raynaud's phenomenon. She has no significant past medical history. She does not take any regular medications.
    Examination reveals dusky coloured digits on her hands and feet. There is no ulceration or skin hardening.

    Blood tests:

    Hb123 g/LMale: (135-180)
    Female: (115 - 160)
    Platelets189 * 109/L(150 - 400)
    WBC4.5 * 109/L(4.0 - 11.0)
    Na+138 mmol/L(135 - 145)
    K+4.2 mmol/L(3.5 - 5.0)
    Urea5.2 mmol/L(2.0 - 7.0)
    Creatinine89 µmol/L(55 - 120)
    CRP4 mg/L(< 5)
    ESR94 mm/hr(0-20)
    IgA2.1 g/L(0.8 - 3.0)
    IgM12.1 g/L(0.4 - 2.5L)
    IgG14.2 g/L(6.0-16.0)
    Antinuclear antibody (ANA)negative(negative)
    Rheumatoid factornegative(negative)

    What is the most likely diagnosis?

    Answer:

    1. Raynaud's - Type I cryoglobulinaemia Type 1 cryoglobulinaemia is the correct answer. The patient presents with Raynaud's phenomenon (RP). Her IgM is significantly raised suggesting a diagnosis of Waldenstrom's macroglobulinaemia. Type 1 cryoglobulinaemia is the only form of cryoglobulinaemia causing Raynaud's phenomenon and it is associated with Waldenstrom's macroglobulinaemia.

    Systemic lupus erythematosus is incorrect. This can cause RP. However, a positive ANA is an entry criterion to be classified as having this condition and therefore this is not likely.

    Limited systemic sclerosis is incorrect. This is a cause of secondary RP but the negative ANA and absence of skin findings make this less likely.

    Type 2 cryoglobulinaemia is incorrect. This condition does not cause RP. Additionally, rheumatoid factor is invariably positive. It is associated with hepatitis C, rheumatoid arthritis, Sjogren's and lymphoma.

    Type 3 cryoglobulinaemia is incorrect. Again, this does not cause RP. It is associated with Sjogren's and rheumatoid arthritis and rheumatoid factor is typically positive.