Cryoglobulinemia

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Última revisão: 18 Jul 2025

Última atualização: 10 May 2024

Cryoglobulinemia may be asymptomatic or present acutely.

Mixed cryoglobulinemia (MC) is the most common type, and it is strongly associated with chronic 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.

Definição

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 (e.g., Waldenstrom macroglobulinemia). Types II and III (MC) may be associated with infectious (most commonly hepatitis C virus [HCV] infection) or autoimmune disorders.[1][2] 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.[3][4]

História e exame físico

Principais fatores diagnósticos

arthralgia
weakness
vasculitis
lower-extremity vascular purpura

Detalhes completos

Outros fatores diagnósticos

peripheral neuropathy
sicca symptoms
hypertension
Raynaud phenomenon
lower extremity skin ulcers
diplopia
ataxia
headache
confusion
retinal hemorrhage/retinal vein thrombosis
acrocyanosis

Detalhes completos

Fatores de risco

hepatitis C virus (HCV) infection
other viral infections
autoimmune disorders
lymphoproliferative disorders

Detalhes completos

Investigações diagnósticas

Primeiras investigações a serem solicitadas

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

Detalhes completos

Investigações a serem consideradas

HIV antibody
antinuclear antibody (ANA), Sjogren syndrome antigens, extractable nuclear antigen (ENA) antibody
skin biopsy

Detalhes completos

Algoritmo de tratamento

AGUDA

mixed cryoglobulinemia

malignancy-associated cryoglobulinemia (type I)

Colaboradores

Autores

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

Declarações

GSK declares that he has no competing interests.

Revisores

Morie Gertz, MD

Professor of Medicine

Division of Hematology

Mayo Clinic

Rochester

Declarações

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

Declarações

AP declares that he has no competing interests.

Xavier Leleu, MD, PhD

Instructor in Hematology

Department of Hematology

Hopital Huriez CHRU

Lille

France

Declarações

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

Declarações

RM declares that he has no competing interests.

Referências

Nossas equipes internas de editoria e de evidências trabalham em conjunto com colaboradores internacionais especializados e pares revisores para garantir que forneçamos acesso às informações o mais clinicamente relevantes possível.

Principais artigos

Ferri C. Mixed cryoglobulinemia. Orphanet J Rare Dis. 2008 Sep 16;3:25.Texto completo Resumo

Roccatello D, Saadoun D, Ramos-Casals M, et al. Cryoglobulinaemia. Nat Rev Dis Primers. 2018 Aug 2;4(1):11. Resumo

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].Texto completo

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.Texto completo Resumo

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.Texto completo Resumo

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.Texto completo

Artigos de referência

Uma lista completa das fontes referenciadas neste tópico está disponível para os usuários com acesso total ao BMJ Best Practice.

Diagnósticos diferenciais
- Small to medium vessel vasculitis
- Cryofibrinogenemia
Mais Diagnósticos diferenciais
Diretrizes
- Management of mixed cryoglobulinemia with rituximab
- Prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease
Mais Diretrizes
Folhetos informativos para os pacientes
Hepatitis C: what is it?
Hepatitis C: what treatments work?
Mais Folhetos informativos para os pacientes
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Cryoglobulinemia

Resumo

Definição

História e exame físico

Principais fatores diagnósticos

Outros fatores diagnósticos

Fatores de risco

Investigações diagnósticas

Primeiras investigações a serem solicitadas

Investigações a serem consideradas

Algoritmo de tratamento

mixed cryoglobulinemia

malignancy-associated cryoglobulinemia (type I)

Colaboradores

Autores

Gurjit S. Kaeley, MBBS, MRCP

Declarações

Revisores

Morie Gertz, MD

Declarações

Antonio Palumbo, MD

Declarações

Xavier Leleu, MD, PhD

Declarações

Rajan Madhok, MD, FCRP

Declarações

Referências

Principais artigos

Artigos de referência

Uma lista completa das fontes referenciadas neste tópico está disponível para os usuários com acesso total ao BMJ Best Practice.

Diagnósticos diferenciais

Diretrizes

Folhetos informativos para os pacientes

Conectar-se ou assinar para acessar todo o BMJ Best Practice

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