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)
Gurjit S. Kaeley, MBBS, MRCP
Professor of Medicine
Chief, Division of Rheumatology and Clinical Immunology
Medical Director, Musculoskeletal Ultrasound Program
Program Director, Rheumatology Fellowship
University of Florida College of Medicine - Jacksonville
GSK declares that he has no competing interests.
Dina Titova, MD, PhD
DT has received a fee from an educational grant from the Center of Excellence for organizing CME South Sound Bond Club conference.
Antonio Palumbo, MD
University of Turin
AP declares that he has no competing interests.
Xavier Leleu, MD, PhD
Instructor in Hematology
Department of Hematology
Hopital Huriez CHRU
XL has received lecture fees and research funding from Janssen-Cilag, Celgene, Chugai, Amgen, Novartis, Mundipharma, and Roche. XL is an author of a number of references cited in this topic.
Rajan Madhok, MD, FCRP
Consultant Physician and Rheumatologist
Centre for Rheumatic Diseases
Glasgow Royal Infirmary
RM declares that he has no competing interests.
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