BACK TOTOP Browse A-ZSearchBrowse A-ZABCDEFGHIJKLMNOPQRSTUVWXYZ0-9 E-mail FormEmail ResultsName:Email address:Recipients Name:Recipients address:Message: Print-FriendlyBookmarksbookmarks-menuCryoglobulinemiaCryoglobulinemia is the presence of abnormal proteins in the blood. These proteins thicken in cold temperatures.ProteinsProteins are the building blocks of life. Every cell in the human body contains protein. The basic structure of protein is a chain of amino acids. ...ImageRead Article Now Book Mark Article Causes Cryoglobulins are antibodies. It is not yet known why they become solid or gel-like at low temperatures in the laboratory. In the body, these antibodies can form immune complexes that can cause inflammation and block blood vessels. This is called cryoglobulinemic vasculitis. This may lead to problems ranging from skin rashes to kidney failure.AntibodiesAn antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include micr...ImageRead Article Now Book Mark Article Cryoglobulinemia is part of a group of diseases that cause damage and inflammation of the blood vessels throughout the body (vasculitis). There are three main types of this condition. They are grouped based on the type of antibody that is produced:Type I Type II Type IIIType I cryoglobulinemia is most often related to cancer of the blood or immune systems.Types II and III are also referred to as mixed cryoglobulinemia.Types II and III are most often found in people who have a long-lasting (chronic) inflammatory condition, such as an autoimmune disease or hepatitis C. Most people with the type II form of cryoglobulinemia have a chronic hepatitis C infection.Autoimmune diseaseAn autoimmune disorder occurs when the body's immune system attacks and destroys healthy body tissue by mistake. There are more than 80 autoimmune d...ImageRead Article Now Book Mark Article Other conditions that may be related to cryoglobulinemia include:Leukemia Multiple myeloma Primary macroglobulinemia Rheumatoid arthritis Rheumatoid arthritisRheumatoid arthritis (RA) is a disease that leads to inflammation of the joints and surrounding tissues. It is a long-term disease. It can also aff...ImageRead Article Now Book Mark Article Systemic lupus erythematosusSystemic lupus erythematosusSystemic lupus erythematosus (SLE) is an autoimmune disease. In this disease, the immune system of the body mistakenly attacks healthy tissue. It c...ImageRead Article Now Book Mark Article Symptoms Symptoms will vary, depending on the type of disorder you have and the organs that are involved. Symptoms may include: Breathing problems Fatigue Glomerulonephritis (kidney inflammation) GlomerulonephritisGlomerulonephritis is a type of kidney disease in which the part of your kidneys that helps filter waste and fluids from the blood is damaged....ImageRead Article Now Book Mark Article Joint pain Muscle pain Purpura PurpuraPurpura is purple-colored spots and patches that occur on the skin, and in mucus membranes, including the lining of the mouth.ImageRead Article Now Book Mark Article Raynaud phenomenon Raynaud phenomenonRaynaud phenomenon is a condition in which cold temperatures or strong emotions cause blood vessel spasms. This blocks blood flow to the affected re...ImageRead Article Now Book Mark Article Skin death Skin ulcers Exams and Tests The health care provider will do a physical exam. You will be checked for signs of liver and spleen swelling.Tests for cryoglobulinemia include:Complete blood count (CBC). Complete blood countA complete blood count (CBC) test measures the following:The number of white blood cells (WBC count)The number of red blood cells (RBC count)The numb...ImageRead Article Now Book Mark Article Complement assay -- complement levels will be low. Complement assayComplement is a blood test that measures the activity of certain proteins in the liquid portion of your blood. The complement system is a group of ne...ImageRead Article Now Book Mark Article Cryoglobulin test -- may show presence of cryoglobulins. (This is a complicated laboratory procedure that involves many steps. It is important that the lab that performs the test is familiar with the process.) Cryoglobulin testCryoglobulins are antibodies that become solid or gel-like at low temperatures in the laboratory. This article describes the blood test used to chec...ImageRead Article Now Book Mark Article Liver function tests -- may be high if hepatitis C is present. Liver function testsLiver function tests are common tests that are used to see how well the liver is working. Tests include:AlbuminAlpha-1 antitrypsinAlkaline phosphata...ImageRead Article Now Book Mark Article Rheumatoid factor -- positive in types II and III. Rheumatoid factorRheumatoid factor (RF) is a blood test that measures the amount of the RF antibody in the blood.ImageRead Article Now Book Mark Article Skin biopsy -- may show inflammation in blood vessels, vasculitis. BiopsyA biopsy is the removal of a small piece of tissue for laboratory examination.Read Article Now Book Mark Article Protein electrophoresis - blood -- may show an abnormal antibody protein. Protein electrophoresis - bloodThis lab test measures the types of protein in the fluid (serum) part of a blood sample. This fluid is called serum.ImageRead Article Now Book Mark Article Urinalysis -- may show blood in the urine if the kidneys are affected. Blood in the urineBlood in your urine is called hematuria. The amount may be very small and only detected with urine tests or under a microscope. In other cases, the...ImageRead Article Now Book Mark Article Other tests may include:Angiogram AngiogramAn arteriogram is an imaging test that uses x-rays and a special dye to see inside the arteries. It can be used to view arteries in the heart, brain...ImageRead Article Now Book Mark Article Chest x-ray ESR ESRESR stands for erythrocyte sedimentation rate. It is commonly called a "sed rate. "It is a test that indirectly measures the level of certain protei...ImageRead Article Now Book Mark Article Hepatitis C test Nerve conduction tests, if the person has numbness or weakness in the arms or legs Treatment MIXED CRYOGLOBULINEMIA (TYPES II AND III)Mild or moderate forms of cryoglobulinemia can often be treated by taking steps to deal with the underlying cause.Current direct-acting medicines for hepatitis C eliminate the virus in nearly all people. As hepatitis C goes away, the cryoglobulins will disappear in about one half of all people over the next 12 months. Your provider will continue to monitor the cryoglobulins after treatment.Severe cryoglobulinemia vasculitis involves vital organs or large areas of skin. It is treated with corticosteroids and other medicines that suppress the immune system.Rituximab is an effective drug and has fewer risks than other medicines. Cyclophosphamide is used in life-threatening conditions where rituximab is not working or available. This medicine was used more often in the past. A treatment called plasmapheresis is also used. In this procedure, blood plasma is taken out of blood circulation and abnormal cryoglobulin antibody proteins are removed. The plasma is replaced by fluid, protein, or donated plasma.TYPE I CRYOGLOBULINEMIAThis disorder is due to a cancer of the blood or immune system such as multiple myeloma. Treatment is directed against the abnormal cancer cells that produce the cryoglobulin.Multiple myelomaHemophilia A is a hereditary bleeding disorder caused by a lack of blood clotting factor VIII. Without enough factor VIII, the blood cannot clot pro...ImageRead Article Now Book Mark Article Outlook (Prognosis) Most of the time, mixed cryoglobulinemia does not lead to death. Outlook can be poor if the kidneys are affected. Possible Complications Complications include: Bleeding in the digestive tract (rare) Heart disease (rare) Skin infections or ulcers Kidney failure Liver failure Skin death Death When to Contact a Medical Professional Contact your provider if:You develop symptoms of cryoglobulinemia. You have hepatitis C and develop symptoms of cryoglobulinemia. You have cryoglobulinemia and develop new or worsening symptoms. Prevention There is no known prevention for the condition. Staying away from cold temperatures may prevent some symptoms. Testing and treatment for hepatitis C infection will reduce your risk.Open ReferencesReferencesDiGuardo MA, Bobr A, Winters JL. Hemapheresis. In: McPherson RA, Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory Methods. 24th ed. Philadelphia, PA: Elsevier; 2022:chap 38.Roccatello D, Saadoun D, Ramos-Casals M, et al. Cryoglobulinaemia. Nat Rev Dis Primers. 2018;4(1):11. PMID: 30072738 pubmed.ncbi.nlm.nih.gov/30072738/.Stone JH. Immune complex-mediated small-vessel vasculitis. In: Firestein GS, Budd RC, Gabriel SE, Koretzky GA, McInnes IB, O'Dell JR, eds. Firestein & Kelley's Textbook of Rheumatology. 11th ed. Philadelphia, PA: Elsevier; 2021:chap 96.AllVideoImagesTogCryoglobulinemia of the fingers - illustration Cryoglobulinemia is caused by an abnormal protein that is occasionally found in the blood of people with multiple myeloma, leukemia, and certain forms of pneumonia. It causes blood to gel at low temperatures. In this picture, cryoglobulinemia has reduced blood flow in the fingers so much the fingers have turned dark. The black areas are gangrene resulting from lack of blood flow.Cryoglobulinemia of the fingersillustrationCryoglobulinemia - fingers - illustration Tissue necrosis caused by distal capillary thrombosis resulting from cryoglobulin precipitation in the vessels. The black tissue under the nails is ischemic, and will eventually slough, or be reabsorbed by the body.Cryoglobulinemia - fingersillustrationBlood cells - illustration Blood is comprised of red blood cells, platelets, and various white blood cells.Blood cellsillustrationCryoglobulinemia of the fingers - illustration Cryoglobulinemia is caused by an abnormal protein that is occasionally found in the blood of people with multiple myeloma, leukemia, and certain forms of pneumonia. It causes blood to gel at low temperatures. In this picture, cryoglobulinemia has reduced blood flow in the fingers so much the fingers have turned dark. The black areas are gangrene resulting from lack of blood flow.Cryoglobulinemia of the fingersillustrationCryoglobulinemia - fingers - illustration Tissue necrosis caused by distal capillary thrombosis resulting from cryoglobulin precipitation in the vessels. The black tissue under the nails is ischemic, and will eventually slough, or be reabsorbed by the body.Cryoglobulinemia - fingersillustrationBlood cells - illustration Blood is comprised of red blood cells, platelets, and various white blood cells.Blood cellsillustrationRelated Information Protein in diet(Nutrition)Mycoplasma pneumonia(Condition)Autoimmune disorders(Condition)Systemic lupus erythematosus(Condition)Rheumatoid arthritis(Condition)Cryoglobulins(Medical Test)Pneumonia - InDepth(In-Depth)Systemic lupus erythematosus - InDepth(In-Depth)Rheumatoid arthritis - InDepth(In-Depth) Review Date: 1/25/2023 Reviewed By: Neil J. Gonter, MD, Assistant Professor of Medicine, Columbia University, NY and private practice specializing in Rheumatology at Rheumatology Associates of North Jersey, Teaneck, NJ. Review provided by VeriMed Healthcare Network. Also reviewed by David C. Dugdale, MD, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team. 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CryoglobulinemiaCryoglobulinemia is the presence of abnormal proteins in the blood. These proteins thicken in cold temperatures.ProteinsProteins are the building blocks of life. Every cell in the human body contains protein. The basic structure of protein is a chain of amino acids. ...ImageRead Article Now Book Mark Article Causes Cryoglobulins are antibodies. It is not yet known why they become solid or gel-like at low temperatures in the laboratory. In the body, these antibodies can form immune complexes that can cause inflammation and block blood vessels. This is called cryoglobulinemic vasculitis. This may lead to problems ranging from skin rashes to kidney failure.AntibodiesAn antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include micr...ImageRead Article Now Book Mark Article Cryoglobulinemia is part of a group of diseases that cause damage and inflammation of the blood vessels throughout the body (vasculitis). There are three main types of this condition. They are grouped based on the type of antibody that is produced:Type I Type II Type IIIType I cryoglobulinemia is most often related to cancer of the blood or immune systems.Types II and III are also referred to as mixed cryoglobulinemia.Types II and III are most often found in people who have a long-lasting (chronic) inflammatory condition, such as an autoimmune disease or hepatitis C. Most people with the type II form of cryoglobulinemia have a chronic hepatitis C infection.Autoimmune diseaseAn autoimmune disorder occurs when the body's immune system attacks and destroys healthy body tissue by mistake. There are more than 80 autoimmune d...ImageRead Article Now Book Mark Article Other conditions that may be related to cryoglobulinemia include:Leukemia Multiple myeloma Primary macroglobulinemia Rheumatoid arthritis Rheumatoid arthritisRheumatoid arthritis (RA) is a disease that leads to inflammation of the joints and surrounding tissues. It is a long-term disease. It can also aff...ImageRead Article Now Book Mark Article Systemic lupus erythematosusSystemic lupus erythematosusSystemic lupus erythematosus (SLE) is an autoimmune disease. In this disease, the immune system of the body mistakenly attacks healthy tissue. It c...ImageRead Article Now Book Mark Article Symptoms Symptoms will vary, depending on the type of disorder you have and the organs that are involved. Symptoms may include: Breathing problems Fatigue Glomerulonephritis (kidney inflammation) GlomerulonephritisGlomerulonephritis is a type of kidney disease in which the part of your kidneys that helps filter waste and fluids from the blood is damaged....ImageRead Article Now Book Mark Article Joint pain Muscle pain Purpura PurpuraPurpura is purple-colored spots and patches that occur on the skin, and in mucus membranes, including the lining of the mouth.ImageRead Article Now Book Mark Article Raynaud phenomenon Raynaud phenomenonRaynaud phenomenon is a condition in which cold temperatures or strong emotions cause blood vessel spasms. This blocks blood flow to the affected re...ImageRead Article Now Book Mark Article Skin death Skin ulcers Exams and Tests The health care provider will do a physical exam. You will be checked for signs of liver and spleen swelling.Tests for cryoglobulinemia include:Complete blood count (CBC). Complete blood countA complete blood count (CBC) test measures the following:The number of white blood cells (WBC count)The number of red blood cells (RBC count)The numb...ImageRead Article Now Book Mark Article Complement assay -- complement levels will be low. Complement assayComplement is a blood test that measures the activity of certain proteins in the liquid portion of your blood. The complement system is a group of ne...ImageRead Article Now Book Mark Article Cryoglobulin test -- may show presence of cryoglobulins. (This is a complicated laboratory procedure that involves many steps. It is important that the lab that performs the test is familiar with the process.) Cryoglobulin testCryoglobulins are antibodies that become solid or gel-like at low temperatures in the laboratory. This article describes the blood test used to chec...ImageRead Article Now Book Mark Article Liver function tests -- may be high if hepatitis C is present. Liver function testsLiver function tests are common tests that are used to see how well the liver is working. Tests include:AlbuminAlpha-1 antitrypsinAlkaline phosphata...ImageRead Article Now Book Mark Article Rheumatoid factor -- positive in types II and III. Rheumatoid factorRheumatoid factor (RF) is a blood test that measures the amount of the RF antibody in the blood.ImageRead Article Now Book Mark Article Skin biopsy -- may show inflammation in blood vessels, vasculitis. BiopsyA biopsy is the removal of a small piece of tissue for laboratory examination.Read Article Now Book Mark Article Protein electrophoresis - blood -- may show an abnormal antibody protein. Protein electrophoresis - bloodThis lab test measures the types of protein in the fluid (serum) part of a blood sample. This fluid is called serum.ImageRead Article Now Book Mark Article Urinalysis -- may show blood in the urine if the kidneys are affected. Blood in the urineBlood in your urine is called hematuria. The amount may be very small and only detected with urine tests or under a microscope. In other cases, the...ImageRead Article Now Book Mark Article Other tests may include:Angiogram AngiogramAn arteriogram is an imaging test that uses x-rays and a special dye to see inside the arteries. It can be used to view arteries in the heart, brain...ImageRead Article Now Book Mark Article Chest x-ray ESR ESRESR stands for erythrocyte sedimentation rate. It is commonly called a "sed rate. "It is a test that indirectly measures the level of certain protei...ImageRead Article Now Book Mark Article Hepatitis C test Nerve conduction tests, if the person has numbness or weakness in the arms or legs Treatment MIXED CRYOGLOBULINEMIA (TYPES II AND III)Mild or moderate forms of cryoglobulinemia can often be treated by taking steps to deal with the underlying cause.Current direct-acting medicines for hepatitis C eliminate the virus in nearly all people. As hepatitis C goes away, the cryoglobulins will disappear in about one half of all people over the next 12 months. Your provider will continue to monitor the cryoglobulins after treatment.Severe cryoglobulinemia vasculitis involves vital organs or large areas of skin. It is treated with corticosteroids and other medicines that suppress the immune system.Rituximab is an effective drug and has fewer risks than other medicines. Cyclophosphamide is used in life-threatening conditions where rituximab is not working or available. This medicine was used more often in the past. A treatment called plasmapheresis is also used. In this procedure, blood plasma is taken out of blood circulation and abnormal cryoglobulin antibody proteins are removed. The plasma is replaced by fluid, protein, or donated plasma.TYPE I CRYOGLOBULINEMIAThis disorder is due to a cancer of the blood or immune system such as multiple myeloma. Treatment is directed against the abnormal cancer cells that produce the cryoglobulin.Multiple myelomaHemophilia A is a hereditary bleeding disorder caused by a lack of blood clotting factor VIII. Without enough factor VIII, the blood cannot clot pro...ImageRead Article Now Book Mark Article Outlook (Prognosis) Most of the time, mixed cryoglobulinemia does not lead to death. Outlook can be poor if the kidneys are affected. Possible Complications Complications include: Bleeding in the digestive tract (rare) Heart disease (rare) Skin infections or ulcers Kidney failure Liver failure Skin death Death When to Contact a Medical Professional Contact your provider if:You develop symptoms of cryoglobulinemia. You have hepatitis C and develop symptoms of cryoglobulinemia. You have cryoglobulinemia and develop new or worsening symptoms. Prevention There is no known prevention for the condition. Staying away from cold temperatures may prevent some symptoms. Testing and treatment for hepatitis C infection will reduce your risk.Open ReferencesReferencesDiGuardo MA, Bobr A, Winters JL. Hemapheresis. In: McPherson RA, Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory Methods. 24th ed. Philadelphia, PA: Elsevier; 2022:chap 38.Roccatello D, Saadoun D, Ramos-Casals M, et al. Cryoglobulinaemia. Nat Rev Dis Primers. 2018;4(1):11. PMID: 30072738 pubmed.ncbi.nlm.nih.gov/30072738/.Stone JH. Immune complex-mediated small-vessel vasculitis. In: Firestein GS, Budd RC, Gabriel SE, Koretzky GA, McInnes IB, O'Dell JR, eds. Firestein & Kelley's Textbook of Rheumatology. 11th ed. Philadelphia, PA: Elsevier; 2021:chap 96.