Refers to the presence of cryoglobulins in the serum. Cryoglobulins are immunoglobulins that reversibly precipitate at temperatures below 98.6°F (37°C).
Type I cryoglobulinemia is mostly associated with lymphoproliferative disorders (e.g., Waldenstrom macroglobulinemia); types II and III (mixed cryoglobulinemia [MC]) with autoimmune and infectious conditions, particularly with hepatitis C virus (HCV) infection.
Clinical presentation includes a triad of purpura, weakness, and arthralgia. Multisystemic involvement may include the kidneys, liver, and nervous system.
Diagnosis is based on clinical and laboratory findings. Leukocytoclastic vasculitis is the histologic hallmark of MC.
Management of MC secondary to chronic HCV infection includes viral eradication strategies in addition to immunosuppression.
Cryoglobulinemia refers to the presence of cryoglobulins in the serum. Cryoglobulins are immunoglobulins that reversibly precipitate at temperatures below 98.6°F (37°C). Type I cryoglobulinemia is usually associated with lymphoproliferative disorders. Types II and III may be associated with infectious (hepatitis C virus infection) or autoimmune disorders. The clinical presentation includes a triad of purpura, weakness, and arthralgia. Multisystemic 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
- lower-extremity vascular purpura
Other diagnostic factors
- peripheral neuropathy
- sicca symptoms
- Raynaud phenomenon
- lower extremity skin ulcers
- retinal hemorrhage/retinal vein thrombosis
- hepatitis C virus (HCV) infection
- other viral infections
- autoimmune disorders
- lymphoproliferative disorders
1st investigations to order
- fasting qualitative serum cryoglobulins
- comprehensive chemistry panel
- 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 syndrome antigens, extractable nuclear antigen (ENA) antibody
- skin biopsy
malignancy-associated cryoglobulinemia (type I)
- Small to medium vessel vasculitis
- The management of chronic hepatitis C: 2018 guideline update from the Canadian Association for the Study of the Liver
- Recommendations on treatment of hepatitis C 2018
Hepatitis C: what is it?
Hepatitis C: what treatments work?More Patient leaflets
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