Cryoglobulinemia is a disease caused by increased Cryoglobulins in serum. Excessive amounts of abnormal proteins-cryoglobulins in blood become thick and viscous at lower body temperature. The viscous and thick blood increases blood viscosity and causes blocking blood vessels resulting in many serious complications. In this article, we will discuss about the causes, symptoms, and treatments for Cryoglobulinemia.


How Is Cryoglobulinemia Defined?

  • It is a pathological condition in which there are excessive amounts of cryoglobulins in the blood, which have a tendency to become thick at low temperatures.
  • Cryoglobulinemia is also known to be associated with other diseases like multiple myeloma and hepatitis C.
  • It causes systemic vasculitis, which may cause systemic disease.1

Describe The Causes Of Cryoglobulinemia?

  • Hyper-Viscosity- Cryoglobulins circulates in blood and become thick and precipitate at low body temperature. The cause of change in physical characteristics at low temperature is not known.
  • Antibodies- Cryoglobulins are proteins that function as antibodies. Cryoglobulin increases in autoimmune disease.
  • Infection- Cryoglobulin is found in higher concentration in hepatitis C infection.
  • Blood Cancers- Cryoglobulin is abnormally increased in patient suffering with lymphoma and multiple myeloma
  • Connective Tissue Disease- Concentration of Cryoglobulin is at higher level in patients suffering with connective tissue disorder like lupus.

What Are The Types Of Cryoglobulinemia?

Cryoglobulinemia is basically classified into three types, Type-I, Type-II, and Type-III.

  • Type I Cryoglobulinemia: This is caused by monoclonal immunoglobulin. This type is usually related to cancerous conditions of the blood or the immune systems.
  • Types II Cryoglobulinemia: This is caused by IgM, IgG and IgA monoclonal immunoglobulin. These types of Cryoglobulinemia are most commonly found in people who have chronic inflammatory conditions like hepatitis C.
  • Types III Cryoglobulinemia: This disease is caused by IgM and IgG polyclonal immunoglobulin.

Which Diseases Are Associated With Cryoglobulinemia?

Following diseases often have increased level of Cryoglobulins in blood2-

  • Leukemia
  • Multiple Myeloma
  • Primary Macroglobulinemia
  • Rheumatoid Arthritis
  • Systemic Lupus Erythematosus
  • Mycoplasma Pneumonia
  • Post Streptococcal Glomerulonephritis

Describe The Effects Of Cryoglobulinemia On Organs?

  • Ischemic Changes- Serum Cryoglobulin causes thick precipitation of serum at low temperatures. Increased blood viscosity eventually start slowing the blood flow or blocks the smaller vessels. The reduced blood supply to tissue and organs causes ischemia (lack of blood supply) and numerous complications including renal failure.
  • Tissue and Organ Damage- Cryoglobulinemia is a disease, which damages the tissue secondary to ischemia. Blocking of blood supply to normal tissue and organ causes ischemia.

What Are Some Of The Symptoms Of Cryoglobulinemia?

Patient may be asymptomatic with abnormal blood test suggesting presence of abnormal Cryoglobulin in serum. Symptoms of Cryoglobulinemia, non-specific and systemic, depends on target organ involved in disease.

Non-Specific Symptoms Of Cryoglobulinemia -

  • Fatigue
  • Weight loss

Specific Symptoms of Cryoglobulinemia3 -

  • Skin- Purple bruises, rash and skin ulcer
  • Skeletal System- Joint pain, muscle ache, ankle swelling (edema feet) and Raynaud's phenomenon
  • Nervous System- Peripheral neuropathy3, numbness and weakness
  • Respiratory System- Dyspnea or short of breath
  • Kidney- Glomerulonephritis causes hematuria, proteinuria and kidney failure
  • Cardiovascular System- Hypertension
  • Gastrointestinal System- Enlarged liver and spleen

How Is Cryoglobulinemia Diagnosed?

Clinical Examination

  • Hepatomegaly- Liver enlargement
  • Hypertension- Increased blood pressure
  • Splenomegaly- Enlarged spleen,
  • Numbness- Peripheral neuropathy and numbness

Lab Studies for Cryoglobulinemia

Blood Examination

  • CBC- Results are often normal
  • ESR- Erythrocyte sedimentation rate is increased in Cryoglobulinemia.
  • Complement panel, in case of Cryoglobulinemia the values will be low normal.
  • Cryoglobulin test to look for presence of Cryoglobulins
  • LFTs will be usually high in Cryoglobulinemia.
  • Rheumatoid Factor test is positive.
  • Skin Biopsy- Test is performed if skin ulcer is non-healing.

Urine Examination

  • Urinalysis- Hematuria and proteinuria is observed if patient is suffering with Cryoglobulinemia induced glomerulonephritis.


  • Test is performed to evaluate tissue perfusion.

Chest X-ray

  • X-ray chest is performed to evaluate short of breath and frequent dry cough.

Hepatitis C Test

  • Test is performed to diagnose the cause of pain.

What Is The Treatment For Cryoglobulinemia?

Conservative Treatment for Cryoglobulinemia-

  • Avoid low temperature
  • Patient should move residence to warmer place.

Specific Treatment for Cryoglobulinemia -

  • Corticosteroids4
  • Treatment for Glomerulonephritis-
    • Corticosteroids
    • Immunosuppressive medications
    • Fluid management
    • Electrolyte treatment
    • Kidney dialysis
  • Antibiotics- Rituximab is effective in treating vasculitis caused by cryoglobuminemia.1
  • Plasma Exchange
  • Interferon Alpha

What Are The Complications Of Cryoglobulinemia?

Some of the Complications are:

  • Rare cases of bleeding in digestive tract
  • Rare cases of heart disease
  • Infection of ulcers
  • Renal failure
  • Liver failure


1. Vasculitis neuropathy.

Vrancken AF1, Said G.

Handb Clin Neurol. 2013;115:463-83.

2. Long-term outcome of monoclonal (type 1) cryoglobulinemia.

Néel A1, Perrin F, Decaux O, Dejoie T, Tessoulin B, Halliez M, Mahé B, Lamy T, Fakhouri F, Jego P, Agard C, Vigneau C, Guenet L, Grosbois B, Moreau P, Hamidou M.

Am J Hematol. 2014 Feb;89(2):156-61.

3. Cryoglobulinemia vasculitis: an update.

Terrier B1, Cacoub P.

Curr Opin Rheumatol. 2013 Jan;25(1):10-8.

4. Management of noninfectious mixed cryoglobulinemia vasculitis: data from 242 cases included in the CryoVas survey.

Terrier B1, Krastinova E, Marie I, Launay D, Lacraz A, Belenotti P, de Saint-Martin L, Quemeneur T, Huart A, Bonnet F, Le Guenno G, Kahn JE, Hinschberger O, Rullier P, Diot E, Lazaro E, Bridoux F,

Zénone T, Carrat F, Hermine O, Léger JM, Mariette X, Senet P, Plaisier E, Cacoub P.

Blood. 2012 Jun 21;119(25):5996-6004.

Written, Edited or Reviewed By:


Last Modified On: October 11, 2014

Pain Assist Inc.

Pramod Kerkar
  Note: Information provided is not a substitute for physician, hospital or any form of medical care. Examination and Investigation is necessary for correct diagnosis.

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