Cryoglobulinemia: Epidemiology, Causes, Treatment, Investigations

What is Cryoglobulinemia?

Cryoglobulinemia is a condition in which abnormal proteins in the blood i.e. cryoglobulins clump together forcing the plasma to become thick like maple syrup. These clumps get deposited into blood vessels and limit the flow of blood, block the arteries, increase the risk of blood clots, and damage the muscles, nerves, skin, joints, liver and kidneys. Cryoglobulinemia symptoms may not be constant and keep wavering. Cold temperatures in some cases may act as a trigger in causing flareups.


Although the exact reason for cryoglobulinemia is still not know an autoimmune disorder is referred to as the suspected reason. Other diseases like connective tissue disease, hepatitis C virus infection, liver disease, lymphoma, multiple myeloma and infection could also be related to cryoglobulinemia.

Signs and Symptoms of Cryoglobulinemia

Different symptoms of cryoglobulinemia may be experienced based on the severity and the organs involved. Given below are few of the common symptoms.

Types of Cryoglobulinemia

Cryoglobulinemia Is Broadly Classified Into Three Types:

  • Type I or monoclonal.
  • Type II or mixed – monoclonal and polyclonal.
  • Type III or polyclonal.

Epidemiology of Cryoglobulinemia

Race is not found to be responsible for cryoglobulinemia. Females are more prone to cryoglobulinemia when compared to males. The ratio of cryoglobulinemia between female and male is recorded as 3:1. Cryoglobulinemia usually is seen between the age group of 42 to 52 years.

Causes and Risk Factors of Cryoglobulinemia

  • The exact cause of cryoglobulinemia is still not known, but the suspected cause may implicate towards autoimmune disorders, which are usually responsible for forcing the immune system of the body to attack its own healthy tissues. Cryoglobulinemia often gets activated by cold temperatures.
  • Type I cryoglobulinemia is caused due to lymphoproliferative disorders such as Waldenström macroglobulinemia and multiple myeloma. Type II and type III cryoglobulinemias are usually associated with chronic inflammatory diseases such as infections (chronic hepatitis C virus), coexistent connective-tissue diseases (like SLE, Sjögren syndrome) and chronic liver disease. Lymphoproliferative disorders are seldom the cause of type II cryoglobulinemia.

Treatment for Cryoglobulinemia

  • In cases of mild or moderate cryoglobulinemia, treating the underlying cause generally results in treatment of the disease itself. Cold temperatures are avoided to treat mild cases of cryoglobulinemia.
  • Hepatitis C and mild or moderate cryoglobulinemia are usually treated with standard hepatitis C treatments. Cryoglobulinemia may return back with the discontinuation of the treatment.
  • Corticosteroids and other medications help in suppressing the immune system and treating severe cases of cryoglobulinemia that may involve large areas of skin or vital organs.
  • Plasmapheresis is also used for treating cryoglobulinemia. Plasmapheresis is performed for removing blood plasma from the circulation in order to replace it with protein, fluid and donated plasma.

Investigations for Cryoglobulinemia

A complete subjective and physical examination is performed to diagnose cryoglobulinemia. Cryoglobulinemia may show signs of spleen and liver swelling.

Tests for Diagnosing Cryoglobulinemia Include:

  • Rheumatoid factor.
  • Liver function tests.
  • Complete blood count.
  • Complement assay.
  • Urinalysis.
  • Cryoglobulin test.
  • Skin biopsy.

Other Tests May Include:

  • ESR.
  • Hepatitis C test.
  • Angiogram.
  • Chest x-ray.
  • Protein electrophoresis.
  • Nerve conduction tests.
Team PainAssist
Team PainAssist
Written, Edited or Reviewed By: Team PainAssist, Pain Assist Inc. This article does not provide medical advice. See disclaimer
Last Modified On:July 2, 2021

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