Summary
Definition
History and exam
Key diagnostic factors
- arthralgia
- weakness
- vasculitis
- lower-extremity vascular purpura
Other diagnostic factors
- peripheral neuropathy
- sicca symptoms
- hypertension
- Raynaud phenomenon
- lower extremity skin ulcers
- diplopia
- ataxia
- headache
- confusion
- retinal hemorrhage/retinal vein thrombosis
- acrocyanosis
Risk factors
- hepatitis C virus (HCV) infection
- other viral infections
- autoimmune disorders
- lymphoproliferative disorders
Diagnostic tests
1st tests to order
- fasting qualitative serum cryoglobulins
- CBC
- comprehensive chemistry panel
- erythrocyte sedimentation rate, CRP
- urinalysis
- ECG
- CXR
- rheumatoid factor
- complement CH50, C3, C4
- hepatitis C virus (HCV) antibody
- hepatitis B virus antibody
Tests to consider
- HIV antibody
- antinuclear antibody (ANA), Sjogren syndrome antigens, extractable nuclear antigen (ENA) antibody
- skin biopsy
Treatment algorithm
mixed cryoglobulinemia
malignancy-associated cryoglobulinemia (type I)
Contributors
Authors
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
Jacksonville
FL
Disclosures
GSK declares that he has no competing interests.
Peer reviewers
Morie Gertz, MD
Professor of Medicine
Division of Hematology
Mayo Clinic
Rochester
MN
Disclosures
MG is an author of a number of references cited in this topic.
Antonio Palumbo, MD
Associate Professor
University of Turin
Chief
Myeloma Unit
Ospedale Molinette
Turin
Italy
Disclosures
AP declares that he has no competing interests.
Xavier Leleu, MD, PhD
Instructor in Hematology
Department of Hematology
Hopital Huriez CHRU
Lille
France
Disclosures
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
Glasgow
UK
Disclosures
RM declares that he has no competing interests.
References
Key articles
Roccatello D, Saadoun D, Ramos-Casals M, et al. Cryoglobulinaemia. Nat Rev Dis Primers. 2018 Aug 2;4(1):11. Abstract
American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Oct 2022 [internet publication].Full text
Quartuccio L, Bortoluzzi A, Scirè CA, et al. Management of mixed cryoglobulinemia with rituximab: evidence and consensus-based recommendations from the Italian Study Group of Cryoglobulinemia (GISC). Clin Rheumatol. 2023 Feb;42(2):359-70.Full text Abstract
Montero N, Favà A, Rodriguez E, et al. Treatment for hepatitis C virus-associated mixed cryoglobulinaemia. Cochrane Database Syst Rev. 2018 May 7;(5):CD011403.Full text Abstract
Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C Work Group. KDIGO 2022 clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease. Kidney Int. 2022 Dec;102(6s):S129-205.Full text
Reference articles
A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.
Differentials
- Small to medium vessel vasculitis
- Cryofibrinogenemia
More DifferentialsGuidelines
- Management of mixed cryoglobulinemia with rituximab
- Prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease
More GuidelinesPatient information
Hepatitis C: what is it?
Hepatitis C: what treatments work?
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