Cryoglobulinemia is a rare complication of multiple myeloma and other blood cancers that begin in a type of white blood cell called B cells.

Cryoglobulinemia falls into a group of disorders called vasculitis, which is characterized by inflammation in your blood vessels.

In people with cryoglobulinemia, abnormal proteins called cryoglobulins build up and clump together at temperatures lower than typical body temperature. This clumping restricts blood flow and can lead to damage to your:

  • blood vessels
  • organs
  • muscles

Many people with multiple myeloma who develop cryoglobulinemia experience severe skin symptoms, such as gangrene or areas of dead tissue called necrotic ulcers.

Read on to learn about the connection between cryoglobulinemia and multiple myeloma.

Cryoglobulinemia is when you have many abnormal proteins called cryoglobulins in your blood. In people without cryoglobulinemia, it’s normal for a small number of these proteins to be present.

In cryoglobulinemia, these abnormal proteins clump together at temperatures colder than the typical human body temperature of 37°C (98.6°F). The clumping can block your blood vessels, causing damage to your:

  • blood vessels
  • skin
  • internal organs, especially the liver and kidneys
  • nerves
  • joints

Cryoglobulinemia is divided into types 1, 2, and 3 depending on the makeup of the abnormal protein. Multiple myeloma is associated with type 1 cryoglobulinemia.

Here’s a look at the other conditions associated with cryoglobulinemia:

TypeAssociated conditions
Type 1blood cancers such as:
• multiple myeloma
monoclonal gammopathy of undetermined significance (MGUS)
chronic lymphocytic leukemia
Type 2hepatitis C
• B cell blood disorders
autoimmune diseases
• infectious diseases
Type 3• autoimmune diseases
systemic lupus erythematosus
rheumatoid arthritis
• some infectious diseases

The development of cryoglobulinemia is not completely understood and likely varies between types. Hepatitis C infection is associated with 90 percent of cryoglobulinemia cases.

About 69 to 86 percent of people with type 1 cryoglobulinemia have skin symptoms that can include:

Nearly half of people with type 1 cryoglobulinemia develop severe and potentially life-threatening symptoms like necrotic ulcers or gangrene.

This gallery contains images of cryoglobulinemia rashes on the body.

Other symptoms of cryoglobulinemia

Other symptoms may include:

Some people with cryoglobulinemia do not have any symptoms.

Type 1 cryoglobulinemia is a rare and life-threatening complication of multiple myeloma and other blood cancers that start in B cells. It develops from the abnormal production of cryoglobulin by cancer cells.

The presence of cryoglobulins in multiple myeloma (also called myeloma) was first reported in 1933, and since then, only a few case studies of cryoglobulinemia in people with myeloma have been described in medical literature.

In a 2017 study, researchers studied 102 people who received a diagnosis of type 1 cryoglobulinemia between 1990 and 2015.

The researchers found that 89 of the participants experienced symptoms, and 94 participants had underlying cancer in their lymph system.

The researchers reported:

Underlying conditionParticipants affected
monoclonal gammopathy of undetermined significance (MGUS)38%
lymphoplasmacytic lymphoma21%
multiple myeloma20%
other blood cancer4%
no underlying blood cancer8%

Of the 20 people who had myeloma, 14 had smoldering myeloma. Smoldering myeloma is a precancerous form of myeloma that does not cause symptoms.

MGUS is a noncancerous condition that starts in plasma cells and sometimes becomes myeloma. It generally does not cause symptoms.

Doctors diagnose cryoglobulinemia by considering your symptoms and taking a blood sample for laboratory analysis.

Detection of cryoglobulins and low levels of C4 compartment proteins is typical of cryoglobulinemia.

Cryoglobulinemia is sometimes found incidentally during blood testing when no symptoms are present.

Treatment for cryoglobulinemia is only necessary if you have symptoms.

Because cryoglobulinemia is a rare complication of myeloma, researchers are still investigating the best way to treat it. Current treatments typically focus on the underlying cancer.

Limiting exposure to cold temperatures, especially for your hands and feet, can help reduce symptoms. For example, you may benefit from wearing gloves when opening your fridge or freezer.

Treatment categories

In the 2017 study of 102 people with type 1 cryoglobulinemia, 73 people received treatment. Treatment was broadly divided into the following categories:

  • steroids alone
  • steroids with chemotherapy drugs called alkylating agents
  • the targeted therapy drug rituximab (Rituxan) with or without steroids
  • rituximab and alkylating agents with or without steroids
  • new myeloma drugs, including immunomodulatory drugs and proteasome inhibitors
  • other therapies, such as antimetabolites like azathioprine and methotrexate

The researchers in this study found that symptoms improved in about 80 percent of those who received treatment. Only 21 percent experienced no response to treatment.

In the study, 30 percent of people who were treated received plasmapheresis in their initial therapy. Plasmapheresis is a procedure in which plasma is removed from the blood and replaced with healthy plasma.

The researchers did not find a difference in survival between people who did or didn’t receive plasmapheresis. However, the researchers noted it was hard to draw conclusions about its effectiveness because of the small sample size.

In a 2016 case report, researchers studied a 45-year-old woman who was diagnosed with myeloma and cryoglobulinemia. The woman received the chemotherapy drugs bortezomib (Velcade) and lenalidomide (Revlimid) with the steroid dexamethasone.

Her pain and skin symptoms healed, and at the time of publication, the woman was cancer-free for 30 months.

Cryoglobulinemia can potentially be cured by treating the underlying cancer cells producing abnormal proteins.

Type 1 cryoglobulinemia is not associated with a higher death rate in people with blood cancers.

In the 2017 study, researchers found that 77 percent of the participants with type 1 cryoglobulinemia were still alive at a follow-up approximately 4.2 years after diagnosis.

Younger age and not having neurological symptoms were associated with better survival outcomes.

Cryoglobulinemia is a rare complication of multiple myeloma. It’s caused by the buildup of abnormal proteins in the blood that clump together in temperatures below normal body temperature.

Most people with myeloma who develop cryoglobulinemia experience skin symptoms. They often have severe symptoms such as necrotic ulcers or gangrene. These symptoms can be life threatening and require immediate medical attention.

Contact a doctor if you suspect you have this rare condition.