Refers to the presence of cryoglobulins in the serum. Cryoglobulins are immunoglobulins that reversibly precipitate at temperatures below 37°C (98.6°F).
Type I cryoglobulinaemia is mostly associated with lymphoproliferative disorders (e.g., Waldenstrom's macroglobulinaemia); types II and III (mixed cryoglobulinaemia [MC]) with autoimmune and infectious conditions, particularly with hepatitis C virus (HCV) infection.
Clinical presentation includes a triad of purpura, weakness, and arthralgia. Multi-systemic involvement may include the kidneys, liver, and nervous system.
Diagnosis is based on clinical and laboratory findings. Leukocytoclastic vasculitis is the histological hallmark of MC.
Management of MC secondary to chronic HCV infection includes viral eradication strategies in addition to immunosuppression.
Cryoglobulinaemia refers to the presence of cryoglobulins in the serum. Cryoglobulins are immunoglobulins that reversibly precipitate at temperatures below 37°C (98.6°F). Type l cryoglobulinaemia is usually associated with lymphoproliferative disorders. Types ll and lll may be associated with infectious (hepatitis C virus infection) or autoimmune disorders. The clinical presentation includes a triad of purpura, weakness, and arthralgia. Multi-systemic involvement may occur, particularly affecting the kidneys, liver, and nervous system. Widespread small vessel vasculitis has been demonstrated on post-mortem studies.
History and exam
Key diagnostic factors
- presence of risk factors
- lower-extremity vascular purpura
Other diagnostic factors
- peripheral neuropathy
- sicca symptoms
- Raynaud's phenomenon
- lower-extremity skin ulcers
- retinal haemorrhage/retinal vein thrombosis
- hepatitis C virus (HCV) infection
- other viral infections
- autoimmune disorders
- lymphoproliferative disorders
1st investigations to order
- fasting qualitative serum cryoglobulins
- comprehensive blood chemistry profile
- erythrocyte sedimentation rate, CRP
- rheumatoid factor
- complement CH50, C3, C4
- hepatitis C virus (HCV) antibody
- hepatitis B virus antibody
Investigations to consider
- HIV antibody
- antinuclear antibody (ANA), Sjogren's syndrome antigens, extractable nuclear antigen (ENA) antibody
- skin biopsy
malignancy-associated cryoglobulinaemia (type l)
- Small to medium vessel vasculitis
- Recommendations on treatment of hepatitis C 2018
- HCV guidance: recommendations for testing, managing, and treating hepatitis C
Hepatitis C: what is it?
Hepatitis C: what treatments work?More Patient leaflets
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