Cryoglobulinemia is a disorder of the immune system that leads to the muscular pain, joint pain, death of skin and even death in complicated cases. Read and know all about this disorder, including its various causes, symptoms, treatment options, complications and more.

Cryoglobulinemia Definition

It is a condition that is characterized by the presence of large amounts of abnormal proteins in the bloodstream that turn gel-like or thick in cold temperatures. These proteins are known as Cryoglobulins. The term “Cryoglobulinemia” actually refers to the presence in serum of these immunoglobulins that precipitate at a low temperature.

The name “Cryoglobulinemia” literally stands for “cold antibody in the blood”, indicating the chemical properties of the antibodies that lead to this disorder.

Cryoglobulinemia ICD9 Code

The ICD9 Code for this disorder is 273.2.

Cryoglobulinemia Types

Based on the form of antibody that is produced, the condition has been classified into three major types. These are:

Cryoglobulinemia Type I

It is most often associated to cancer of the immune systems or blood. It is caused by monoclonal antibody, generally IgM. It arises at the same time as cancers of the immune system or blood. This type of cancer involves Waldenstrom’s macroglobulinemia, chronic lymphocytic leukemia and Multiple myeloma.

In less common cases, Type I of the disease involves the kidney. This can happen due to formation of clots, or in very rare cases – a thickening of the walls of the capillary in the glomeruli and an elevation in the

Cryoglobulinemia Type II

It arises in people suffering from an autoimmune condition (such as Systemic Lupus Erythematosus or Rheumatoid Arthritis or other diseases caused by dysfunction of the immune system) or a chronic inflammatory disorder like Hepatitis C.

Cryoglobulinemia Type III

It is similar to Type II. Types II and III are referred to as Mixed Cryoglobulinemia. The majority of individuals with Mixed Cryoglobulinemia suffer from a Chronic Hepatitis C infection. Together, Types II and III account for 75% of all cases of Cryoglobulinemia. They comprise of rheumatoid factor (RF), which is generally IgM. In Type II, the RF is monoclonal. It is polyclonal in Type III.

Both types II and III are related with conditions that have chronic internal inflammation. These disorders include autoimmune conditions like Sjorgen’s syndrome and viruses like HIV or Hepatitis C.

Cryoglobulinemia Incidence

In the United States alone, Essential mixed Cryoglobulinemia affects one out of every 100,000 individuals. It is more prevalent in southern Europe and generally manifests in people between 40 and 60 years of age. The disorder is not known to have any racial predilection. The female to male ration for this disorder is 3:1. The mean reported age for the disorder is 42-52 years.

The exact prevalence of this disease remains unknown as yet. The disorder has a greater prevalence in Southern Europe as compared to Northern Europe or Northern America.

Cryoglobulinemia Symptoms

The signs and symptoms of this disorder tend to vary on the basis of the type of the condition that an individual suffers from as well as the organs that are affected.

The signs may usually include the following:

  • Joint pain
  • Glomerulonephritis
  • Difficulty breathing
  • Fatigue
  • Purpura
  • Muscle pain
  • Skin ulceration
  • Skin death
  • Raynaud’s phenomenon

The disorder has many potential symptoms. This is due to the presence of cyoglobulins in the bloodstream, which can affect almost any type of tissue or organ of the body. The precipitation of these abnormal proteins can lead to an obstruction in any blood vessel of the body. Naturally, the signs and symptoms of the condition tend to depend on the location of blood vessel obstruction. However, some of the symptoms are more common in nature than others.

Cryoglobulinemia and Dermatological Disorders

The skin problems associated with Cryoglobulinemia include the following:

Raynaud’s phenomenon

It refers to a discoloration of the toes and fingers that occurs in case of their exposure to a change in temperature.


This condition is marked by the development of purple spotted rashes on the legs.

Livedo reticularis

It refers to a blotchy purplish discoloration of the skin resulting from impaired circulation.


It is characterized by blueness of the feet and hands that arise due to an obstruction of the small arteries situated towards the end of toes and fingers.

Cryoglobulinemia Causes

The condition results from the presence of high amounts of antibodies, which get solidified at reduced temperatures due to unknown factors. They can obstruct the blood vessels throughout the body due to being thickened or gel-like in form. This may cause complications that can range from kidney failure to skin rashes.

Cryoglobulinemia belongs to a group of disorders that result in Vasculitis and cause swelling and damage to blood vessels throughout the body.

Certain conditions can be related to the development of this disorder. These include:

  • Leukemia
  • Multiple myeloma
  • Rheumatoid arthritis
  • Primary macroglobulinemia
  • Systemic lupus erythematosus
  • Mycoplasma pneumonia

Cryoglobulinemia Risk Factors

Doctors and researchers have not clearly mentioned any risk factors for this disorder. However, certain individuals are found to be more susceptible to the condition. These include people suffering from autoimmune conditions like Systemic Lupus Erythematosus (SLE), rheumatoid arthritis and primary Sjögren’s syndrome as well as individuals affected by infectious diseases like Hepatitis C and HIV. Essential Cryoglobulinemia has been suggested to arise as a result of Hepatitis C.

Cryoglobulinemia Diagnosis

The diagnosis of this disorder begins with a physical examination of sufferers. Doctors look for signs of spleen and liver inflammation during physical testing. They ask patients whether they are experiencing problems like fatigue, joint pain and red or purple spots on the limbs which are typical signs of the disorder.

The diagnostic tests for this disease include the following:

  • Skin biopsy
  • Complete blood count (CBC)
  • Cryoglobulin test, which may show the presence of cryoglobulins
  • Liver function tests, which may show high amounts
  • Rheumatoid factor, may come positive in types II and III
  • Complement assay, which may show low numbers
  • Urinalysis, which may show the presence of blood in the urine in case the kidneys are affected

Other tests may also be used for detecting the disease. These may include the following:

  • ESR
  • Angiogram
  • Hepatitis C test
  • Chest x-ray
  • Protein electrophoresis – blood
  • Nerve conduction tests, to check whether an affected individual is suffering from weakness in the legs or arms

Under a microscope, the glomeruli sample in Types II and III generally exhibit a thickening of the capillary walls in the glomeruli and an elevation in the amount of cells in the body. In some cases, obstruction of the capillary loops from small clots developed by the loose cryoglobulins.

Cryoglobulinemia Differential Diagnosis

The signs and symptoms of this condition appear similar to those of various other disorders. Naturally, physicians should confirm the presence of Cryoglobulinemia by distinguishing its symptoms from those of conditions like:

  • Acute Glomerulonephritis
  • Diffuse Proliferative Glomerulonephritis
  • Chronic Lymphocytic Leukemia
  • Churg-Strauss Syndrome
  • Cirrhosis
  • Giant Cell Arteritis
  • Antiphospholipid Syndrome
  • Goodpasture Syndrome
  • Hemolytic-Uremic Syndrome
  • Hepatitis A
  • Hepatitis B
  • Hepatitis C
  • Microscopic Polyangiitis
  • Multiple Myeloma
  • Viral Hepatitis
  • Non-Hodgkin Lymphoma
  • Serum Sickness
  • Systemic Lupus Erythematosus
  • Polyarteritis Nodosa
  • Sarcoidosis
  • Waldenstrom Hypergammaglobulinemia

Physicians generally confirm the disorder after analyzing the personal and family medical history of sufferers and obtaining results from their blood and urine tests. At times, doctors may conduct biopsy which involves taking small samples of tissue from the body of sufferers.

Cryoglobulinemia Treatment

The treatment of mild forms of the condition depends on its underlying cause. The condition is frequently cured by treating its underlying cause. Mild cases can be cured by preventing exposure to cold temperatures.

In people with Hepatitis C who also suffer from mild or moderate cases of Cryoglobulinemia, standard treatment options for Hepatitis C are generally effective. The condition can, however, show a recurrence when treatment is stopped.

Severe cases of the disease, which involve large regions of skin or vital organs of the body, are cured with corticosteroids and other drugs that suppress the immune system.

Medical treatment for the condition may also involve Plasmapheresis, a technique in which blood plasma is removed from the circulation. It is replaced by donated plasma, protein or fluids.

No effective treatment has yet been determined for cases of Cryoglobulinemia that are associated with Hepatitis C. Short-term use of prednisone, followed by usage of interferon alfa for a period of 6 months, has led to the improvement of liver function. However, relapse of vasculitis and liver disease frequently occurs after stopping the use of interferon alfa.

Cryoglobulinemia Prognosis

The disorder is not usually life-threatening in nature. However, the outcome can be poor in case both the kidneys of a patient are affected. The outcome is worse in sufferers with liver failure, renal disease, malignancies and lymphoproliferative disease. In the majority of cases, the presence of cryoglobulins in the bloodstream does not progress to any life-threatening complication.

Cryoglobulinemia Complications

The possible complications of this disorder include the following:

  • Heart disease (rare)
  • Bleeding in the digestive tract (rare)
  • Liver failure
  • Kidney failure
  • Skin death
  • Infections of ulcers
  • Death

In the late stages of the disorder, hepatic and lymphatic malignancies are possible.

Cryoglobulinemia Prevention

There is no specific way to avoid the development of this disease. Some of its symptoms may be prevented by avoiding exposure to cold temperatures. Many cases of Mixed Cryoglobulinemia are related with Hepatitis C. Due to this reason, preventing an Hepatitis C infection may lower the risk of development of Cryoglobulinemia.

Cryoglobulinemia Pictures

The following pictures about Cryoglobulinemia would give you a visual idea about the condition and help you understand the physical appearance of patients of this disorder more vividly.

Picture of Cryoglobulinemia

Picture 1 – Cryoglobulinemia

Cryoglobulinemia Image

Picture 2 – Cryoglobulinemia Image

If you or any of your family members has developed Hepatitis C and symptoms of Cryoglobulinemia, which are worsening with time, call your medical care provider on an immediate basis. Prompt diagnosis and treatment can help you have an early recovery from this disorder and avoid all possible complications, even life-threatening ones, associated with the condition.


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