Learn About Cryoglobulinemia

What is the definition of Cryoglobulinemia?

Cryoglobulinemia is the presence of abnormal proteins in the blood. These proteins thicken in cold temperatures.

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What are the causes of Cryoglobulinemia?

Cryoglobulins are antibodies. It is not yet known why they become solid or gel-like at low temperatures in the laboratory. In the body, these antibodies can form immune complexes that can cause inflammation and block blood vessels. This is called cryoglobulinemic vasculitis. This may lead to problems ranging from skin rashes to kidney failure.

Cryoglobulinemia is part of a group of diseases that cause damage and inflammation of the blood vessels throughout the body (vasculitis). There are three main types of this condition. They are grouped based on the type of antibody that is produced:

  • Type I
  • Type II
  • Type III

Types II and III are also referred to as mixed cryoglobulinemia.

Type I cryoglobulinemia is most often related to cancer of the blood or immune systems.

Types II and III are most often found in people who have a long-lasting (chronic) inflammatory condition, such as an autoimmune disease or hepatitis C. Most people with the type II form of cryoglobulinemia have a chronic hepatitis C infection.

Other conditions that may be related to cryoglobulinemia include:

  • Leukemia
  • Multiple myeloma
  • Primary macroglobulinemia
  • Rheumatoid arthritis
  • Systemic lupus erythematosus
What are the symptoms of Cryoglobulinemia?

Symptoms will vary, depending on the type of disorder you have and the organs that are involved. Symptoms may include:

  • Breathing problems
  • Fatigue
  • Glomerulonephritis
  • Joint pain
  • Muscle pain
  • Purpura
  • Raynaud phenomenon
  • Skin death
  • Skin ulcers
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What are the current treatments for Cryoglobulinemia?


Mild or moderate forms of cryoglobulinemia can often be treated by taking steps to deal with the underlying cause.

Current direct-acting medicines for hepatitis C eliminate the virus in nearly all people. As hepatitis C goes away, the cryoglobulins will disappear in about one half of all people over the next 12 months. Your provider will continue to monitor the cryoglobulins after treatment.

Severe cryoglobulinemia vasculitis involves vital organs or large areas of skin. It is treated with corticosteroids and other medicines that suppress the immune system.

  • Rituximab is an effective drug and has fewer risks than other medicines.
  • Cyclophosphamide is used in life-threatening conditions where rituximab is not working or available. This medicine was used often in the past.
  • A treatment called plasmapheresis is also used. In this procedure, blood plasma is taken out of blood circulation and abnormal cryoglobulin antibody proteins are removed. The plasma is replaced by fluid, protein, or donated plasma.


This disorder is due to a cancer of the blood or immune system such as multiple myeloma. Treatment is directed against the abnormal cancer cells that produce the cryoglobulin.

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What is the outlook (prognosis) for Cryoglobulinemia?

Most of the time, mixed cryoglobulinemia does not lead to death. Outlook can be poor if the kidneys are affected.

What are the possible complications of Cryoglobulinemia?

Complications include:

  • Bleeding in the digestive tract (rare)
  • Heart disease (rare)
  • Infections of ulcers
  • Kidney failure
  • Liver failure
  • Skin death
  • Death
When should I contact a medical professional for Cryoglobulinemia?

Call your provider if:

  • You develop symptoms of cryoglobulinemia.
  • You have hepatitis C and develop symptoms of cryoglobulinemia.
  • You have cryoglobulinemia and develop new or worsening symptoms.
How do I prevent Cryoglobulinemia?

There is no known prevention for the condition.

  • Staying away from cold temperatures may prevent some symptoms.
  • Testing and treatment for hepatitis C infection will reduce your risk.
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Cryoglobulinemia - fingers
Blood cells
What are the latest Cryoglobulinemia Clinical Trials?
Registry for Adults With Plasma Cell Disorders (PCD's)

Summary: The primary purpose of this protocol is to create a registry of patients with plasma cell disorders (PCDs), including for example the cancer multiple myeloma (MM), who complete the assessment, previously known as a geriatric assessment, as is outlined in this protocol. Secondary objectives include measuring the response rate to participation of patients in this study, assessing patient satisfactio...

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A Prospective Cohort Study of Patients With Plasma Cell Disorders (PCDs) in PKUFH

Summary: The primary aim is to establish a prospective cohort of patients with plasma cell disorders (PCDs). All of the hospitalized PCD patients who are willing to sign the informed consent form (ICF) will be included in this study. Clinical characteristics, treatment options and responses will be collected. Peripheral blood, bone marrow aspirate and urine samples before and after the treatment will banke...

What are the Latest Advances for Cryoglobulinemia?
Cryoglobulinemia and double-filtration plasmapheresis: Personal experience and literature review.
A Review on Extrahepatic Manifestations of Chronic Hepatitis C Virus Infection and the Impact of Direct-Acting Antiviral Therapy.
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Dermatological manifestations of monoclonal gammopathies.
Who are the sources who wrote this article ?

Published Date: January 31, 2021
Published By: Diane M. Horowitz, MD, Rheumatology and Internal Medicine, Northwell Health, Great Neck, NY. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.

What are the references for this article ?

DiGuardo MA, Bobr A, Winters JL. Hemapheresis. In: McPherson RA, Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory Methods. 24th ed. Philadelphia, PA: Elsevier; 2022:chap 38.

Roccatello D, Saadoun D, Ramos-Casals M, et al. Cryoglobulinaemia. Nat Rev Dis Primers. 2018;4(1):11. PMID: 30072738 pubmed.ncbi.nlm.nih.gov/30072738/.

Stone JH. Immune complex-mediated small-vessel vasculitis. In: Firestein GS, Budd RC, Gabriel SE, Koretzky GA, McInnes IB, O’Dell JR, eds. Firestein & Kelley's Textbook of Rheumatology. 11th ed. Philadelphia, PA: Elsevier; 2021:chap 96.