Cryoglobulinemia

Overview

Cryoglobulinemia (kry-o-glob-u-lih-NEE-me-uh) is a rare condition in which atypical blood proteins called cryoglobulins clump together when they get cold. This may happen at body temperatures below 98.6 Fahrenheit (37 Celsius).

These clumps can block blood flow. They also can cause inflammation. This can damage the skin, joints, nerves, kidneys and other organs.

Some people have cryoglobulins in their blood but no symptoms. When cryoglobulins cause inflammation of the blood vessels, it's called cryoglobulinemic vasculitis or cryoglobulin-associated vasculitis. This inflammation can damage tissues and organs.

Treatment for cryoglobulinemia depends on the type and what's causing it.

Types

There are three main types of cryoglobulinemia. Types 2 and 3 together are called mixed cryoglobulinemia because the cryoglobulins contain a mixture of proteins.

• Type 1. This type has one kind of atypical protein, called monoclonal. Type 1 most often is linked to certain blood conditions and cancers.
• Type 2. This type has two types of atypical protein, both monoclonal and polyclonal. Type 2 most often is linked to hepatitis C virus infection.
• Type 3. This type has a mix of polyclonal proteins. Type 3 most often is linked to autoimmune diseases such as rheumatoid arthritis.

Mixed cryoglobulinemia that has no known cause may be called essential mixed cryoglobulinemia. When mixed cryoglobulinemia causes inflammation of the blood vessels and related symptoms or organ damage, it may be called mixed cryoglobulinemia syndrome.

Symptoms

Some people have no symptoms of cryoglobulinemia. For people who have symptoms, the symptoms may come and go.

Symptoms depend on the type of cryoglobulinemia and how it affects the body. When cryoglobulinemic vasculitis develops, it often affects the skin, joints, nerves and kidneys.

Cryoglobulinemia symptoms can include:

• Skin changes. Purple or red-purple spots called purpura often appear on the legs. The spots may look different depending on your skin color. Cryoglobulinemia also can cause a purplish, netlike skin pattern called livedo reticularis and open sores called ulcers.
• Joint and muscle pain. Joint pain is especially common with mixed cryoglobulinemia. Muscle pain also can occur.
• Peripheral neuropathy. Cryoglobulinemia can damage nerves, especially in the hands and feet. This nerve damage is called peripheral neuropathy. It can cause numbness, tingling, pain or weakness.
• Raynaud's disease. The fingers or toes may change color and feel numb or painful when they get cold. This can happen with cryoglobulinemia, particularly type 1.
• Kidney issues. Cryoglobulinemia can cause blood or protein in the urine, high blood pressure and reduced kidney function.

When to seek care

Make an appointment with a healthcare professional if you have symptoms that concern you. This is especially true if you have unexplained purple skin spots, skin sores, numbness or tingling, joint pain, or symptoms that happen again and again when you're exposed to cold temperatures.

When to seek emergency care

Some complications of cryoglobulinemia need emergency care. Type 1 cryoglobulinemia can make the blood too thick or block blood flow. Seek emergency medical care for sudden confusion, vision changes or stroke symptoms. Also seek emergency care if you have signs of severely reduced blood flow to a finger or toe, such as terrible pain or darkening of the skin.

Causes

Cryoglobulinemia can be linked to infections, certain blood conditions and cancers, and autoimmune diseases. The conditions linked to cryoglobulinemia vary by type.

• Infections. Hepatitis C is an important cause of mixed cryoglobulinemia. Other infections linked to cryoglobulinemia include hepatitis B and HIV.
• Blood conditions and cancers. Type 1 cryoglobulinemia most often is linked to certain blood conditions and cancers, including multiple myeloma, Waldenstrom macroglobulinemia, non-Hodgkin lymphoma and chronic lymphocytic leukemia.
• Autoimmune diseases. These are diseases in which the immune system attacks healthy tissue by mistake. Examples linked to cryoglobulinemia include Sjogren disease, lupus and rheumatoid arthritis.

Sometimes no cause is found.

Risk factors

Factors that increase the risk of cryoglobulinemia include having a condition linked to the production of cryoglobulins, the blood proteins that clump together when they get cold. These conditions include chronic hepatitis C infection, some autoimmune diseases, and certain blood conditions and cancers.

Cryoglobulinemia is rare. The age and sex of people who have it vary depending on the type of cryoglobulinemia and what's causing it.

Complications

Cryoglobulinemia can damage the kidneys. Signs of kidney damage can include protein or blood in the urine, high blood pressure and reduced kidney function. In time, kidney failure might happen.

Type 1 cryoglobulinemia also can make the blood too thick or block blood flow in small and medium-sized blood vessels. This can damage skin and other tissues, affect vision and the nervous system, and reduce blood flow to the fingers or toes.

Living with cryoglobulinemia?

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