Cryoglobulinemia is a type of vasculitis (damage and inflammation of your blood vessels) that occurs when abnormal blood proteins called cryoglobulins clump together at cold temperatures. Some people don’t have symptoms and don’t need treatment. But moderate to severe cryoglobulinemia can cause damage to your skin, tissues and organs.


What is cryoglobulinemia?

Cryoglobulinemia is a condition that occurs when abnormal proteins in your blood called cryoglobulins thicken and clump together at cold temperatures. The condition is a type of vasculitis (inflammation of your blood vessels), which can restrict blood flow and cause damage to your skin, nerves, joints, muscles and organs — particularly your kidneys. Another name for cryoglobulinemia is cryoglobulinemic vasculitis.

Cryoglobulinemia types

Cryoglobulins are a kind of antibody. Cryoglobulinemia can be divided into three main types, depending on which kind of antibody your body produces.

Type I cryoglobulinemia is frequently associated with an underlying health condition, such as cancer of your blood or immune system.

Type II cryoglobulinemia and type III cryoglobulinemia are often seen in people with long-term (chronic) inflammatory conditions, such as autoimmune diseases. Type II cryoglobulinemia is very common in people with hepatitis C virus (HCV). Another name for types II and III cryoglobulinemia is mixed cryoglobulinemia.

How common is cryoglobulinemia?

Cryoglobulinemia is a rare condition. But researchers don’t know the exact number of cases because low levels of cryoglobulins can be present without causing symptoms. Researchers estimate that the condition affects about 1 out of every 100,000 people worldwide.


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Symptoms and Causes

What are the symptoms of cryoglobulinemia?

People with cryoglobulinemia may or may not experience symptoms. When symptoms are present, they most commonly include a particular rash called purpura that looks like red spots or purple bruises, usually over your lower legs. You may also have fatigue and joint pain.

Other cryoglobulinemia symptoms may include:

What causes cryoglobulinemia?

Researchers don’t know the exact cause of cryoglobulinemia. But the condition is a type of vasculitis, which is an autoimmune disease. Autoimmune disorders occur when your body’s immune system mistakenly attacks healthy tissue. Factors that may trigger this reaction include:

  • Genetics.
  • Certain medications.
  • Infections and viruses.
  • Environmental factors.

Cryoglobulinemia can be present alone (“idiopathic”), but it’s frequently associated with other diseases, such as:

What are the risk factors?

Cryoglobulinemia affects women and people assigned female at birth (AFAB) more often than people assigned male at birth (AMAB). It also most commonly affects people over the age of 50.


What are the complications of cryoglobulinemia?

Left untreated, cryoglobulinemia can cause permanent skin, tissue and organ damage, including:

Diagnosis and Tests

How is cryoglobulinemia diagnosed?

Your healthcare provider will ask about your medical history and perform a physical exam. They’ll order a specific blood test that detects the presence of cryoglobulins in your blood. Learning the type of cryoglobulins can sometimes help determine the cause and how to treat it.

In addition to this blood test, your provider may request the following to help diagnose your condition:


Management and Treatment

How is cryoglobulinemia treated?

Cryoglobulinemia treatment depends on the organs it affects, the degree of damage and the presence of other medical conditions. It’s very important not only to treat cryoglobulinemia but also to address any other associated disorders. When you treat your other conditions, the symptoms of cryoglobulinemia may improve.

For mild cases of cryoglobulinemia, your healthcare provider may recommend over-the-counter (OTC) anti-inflammatory drugs (NSAIDs) for pain, along with avoiding cold temperatures. They’ll want to monitor your disease with regular checkups.

For more moderate to severe cases of cryoglobulinemia, treatments may include:

  • Immunosuppressive drugs: The mainstay of treatment is corticosteroids such as prednisone, with or without other medications, depending on the affected organ and the extent of involvement.
  • Antiviral medications: If your provider found another medical condition like hepatitis C, they may recommend antiviral therapy. They may also refer you to a hepatologist (liver specialist).
  • Biologics: The biologic rituximab is a common treatment for cryoglobulinemia. Biologics are complex proteins derived from living organisms that target certain parts of your immune system to control inflammation.
  • Plasmapheresis: Another form of treatment that decreases the amount of cryoglobulins in your blood. This procedure, called plasmapheresis, removes cryoglobulins from your plasma (the liquid in your blood). This helps prevent cryoglobulins from clogging your arteries, which blocks blood flow and could lead to a rash and organ damage.

Complications and side effects of treatment

The medications your healthcare provider recommends for the treatment of cryoglobulinemia may cause serious side effects. These side effects include potential bone loss (osteoporosis) and lowering your body’s ability to fight infection. Because of this, it’s important to see your provider for routine checkups. They may be able to prescribe medications to offset the side effects. It’s also important to prevent infection, so talk to your provider about vaccinations to lower your risk of infection.


Can cryoglobulinemia be prevented?

Researchers don’t know the cause of cryoglobulinemia, so there’s no way to prevent the condition. But staying out of the cold may help prevent some symptoms from developing. It’s also important to get tested and treated for hepatitis C infection to reduce your risk.

Outlook / Prognosis

What is the outlook (prognosis) for cryoglobulinemia?

Your prognosis depends on several factors, including:

  • Other underlying conditions.
  • The extent of your organ damage.
  • How well you respond to treatment.

In addition, the severity of the condition varies. Some people don’t have any symptoms or have a very mild case that doesn’t require treatment. For people with moderate to severe cases, prompt diagnosis and treatment can help relieve symptoms and prevent long-term complications. If you haven’t experienced any permanent damage to your organs, your prognosis is very good.

Living With

How do I take care of myself? 

The best way to take care of yourself is to actively work with your healthcare providers. Depending on which organs cryoglobulinemia affects, you may work with a team of specialists that includes:

Get to know the members of your team. And be sure to advocate for yourself. Ask questions. If you have concerns about your treatment plan, speak up. Your providers are there to listen and make sure you fully understand everything that affects your health and care.

When should I see my healthcare provider?

You should seek treatment from your healthcare provider if you develop any of the symptoms of cryoglobulinemia. It’s also important to contact your provider if you have hepatitis C and develop any of the symptoms.

Even with effective treatment, relapses can occur. See your provider if you develop new or worsening symptoms or if your symptoms return. Routine checkups and frequent monitoring are important in finding relapses and preventing complications.

What questions should I ask my healthcare provider?

Questions to ask your healthcare provider include:

  • What caused my condition?
  • What treatments do you recommend?
  • What side effects of the treatment should I watch out for?
  • What complications can this condition cause?
  • What can I do to prevent a relapse?

A note from Cleveland Clinic

Cryoglobulinemia can be a challenging condition to live with. Symptoms of the condition and side effects of your medications can take a great toll on your sense of well-being. It can also affect many other aspects of your life. But you don’t have to go through it alone. Ask your healthcare provider to help you find a support group. Sharing stories and tips with others experiencing cryoglobulinemia may help.

Medically Reviewed

Last reviewed on 09/28/2023.

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