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Different types of cryoglobulinemia have been associated with hepatitis C infection, certain cancers of the blood and autoimmune diseases. Treatment focuses on controlling these underlying diseases and managing symptoms. Symptoms. Symptoms of cryoglobulinemia may include purple spots on the legs, joint pain, and numbness in the fingers and toes.
What is cryoglobulinemia and how is it treated?
Most people with cryoglobulins have no symptoms other than elevated levels on specially ordered lab tests. When symptoms are present, they are most commonly fatigue, joint pain, numbness or weakness, and a particular rash called purpura that looks like red spots or purple bruises, usually over the lower legs.
What are the symptoms of high cryoglobulin levels?
Yes. There are three different types of cryoglobulinemia, type 1, 2, and 3. Lung symptoms are common in type 2 and 3 cryoglobulinemia. Type 2 and 3 disease often occurs in people with an autoimmune disease or hepatitis C infection. Lung symptoms may include shortness of breath, cough, or sharp pain when breathing in and out (pleurisy).
Can cryoglobulinemia cause shortness of breath?
In contrast to these benign instances of circulating cryoglobulins, cryoglobulinemic disease involves the signs and symptoms of precipitating cryoglobulins and is commonly associated with various pre-malignant, malignant, infectious, or autoimmune diseases that are the underlying cause for production of the cryoglobulins. [2] [3]
What is the pathophysiology of cryoglobulinemic disease?
What is cryoglobulinemia caused from?
Hepatitis C is the most common infection associated with cryoglobulinemia. Others include hepatitis B, HIV, Epstein-Barr, toxoplasmosis and malaria. Certain cancers. Some cancers of the blood, such as multiple myeloma, Waldenstrom macroglobulinemia and chronic lymphocytic leukemia, can sometimes cause cryoglobulinemia.
How do I know if I have cryoglobulinemia?
Diagnosis of cryoglobulinemia involves a blood test in which the sample must be kept at normal body temperature, 98.6 F (37 C), for a period of time before being cooled. Inaccurate test results can occur if the blood sample isn't handled properly.
Does cryoglobulinemia go away?
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.
How do I get rid of cryoglobulinemia?
Cryoglobulinemia is commonly treated with corticosteroids such as prednisone, and medications that suppress the immune system. Antiviral drugs are prescribed when HCV is present. Left untreated, the disease can cause permanent tissue and organ damage, so it is important to seek prompt medical care when symptoms appear.
When do you suspect cryoglobulinemia?
The diagnosis of a cryoglobulinemia syndrome should be suspected in patients presenting with arthralgia, purpura, skin ulcers, glomerulonephritis, and peripheral neuropathy.
What kind of doctor treats cryoglobulinemia?
Your treatment team may include specialists in blood (hematologists), connective tissue and arthritis (rheumatologists), liver diseases (hepatologists), the nervous system (neurologists), the kidneys (nephrologists), and other areas as needed.
Is cryoglobulinemia itchy?
Additional nonspecific symptoms are common including mild to severe itching, mild to severe pain, abdominal pain, muscle weakness, muscle pain (myalgia), and abnormal enlargement of the lymph nodes (lymphadenopathy).
What is the blood test for cryoglobulinemia?
A cryoglobulins test is used to help detect the presence and relative quantity of cryoglobulins in the blood. It may be ordered along with other tests to help determine or rule out potential causes of cryoglobulinemia. The tests ordered depend on what condition or disease is suspected.
Can cryoglobulinemia cause neuropathy?
Cryoglobulinemia is a frequent cause of peripheral neuropathy in undiagnosed referral patients.
What does a high Cryoglobulin level mean?
High levels of cryoglobulins may be a sign that your body is making abnormal proteins. This condition is seen with a number of autoimmune disorders and conditions, such as Raynaud syndrome, lupus, rheumatoid arthritis, Sjogren syndrome, leukemia, and lymphoma.
What is vasculitis caused by?
In vasculitis, the immune system attacks blood vessels. Some cases of vasculitis are caused by reactions to medicines. Also, some chronic (long-term) infections, including with hepatitis C or hepatitis B virus, can cause vasculitis.
How do you test for mixed cryoglobulinemia?
A diagnosis of mixed cryoglobulinemia is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a blood test to detect the presence of cryoglobulins.
Can cryoglobulinemia cause neuropathy?
Cryoglobulinemia is a frequent cause of peripheral neuropathy in undiagnosed referral patients.
What is a Cryofibrinogen test for?
What is this test? This test looks for an abnormal protein called cryofibrinogen in your blood plasma. People who have this abnormal protein may get a disorder called cryofibrinogenemia. The disorder rarely causes symptoms.
How does Hep C cause cryoglobulinemia?
Cryoglobulinemia and Hepatitis C The condition most commonly linked with hep C is cryoglobulinemia. This condition is due to the presence of abnormal antibodies (called cryoglobulins) that come from hepatitis C virus stimulation of lymphocytes (white blood cells).
How long does it take to get a cryoglobulin test result?
Learning the type of cryoglobulins can sometimes help determine its cause. It takes almost a week after the test is ordered to get the result.
How to treat rash from cryoglobulins?
Another form of treatment decreases the amount of cryoglobulins in the blood. This procedure, called plasmapheresis, removes cryoglobulins from the plasma (the liquid in the blood). This helps prevent cryoglobulins from clogging the arteries, which blocks blood flow and could lead to the rash and organ damage.
What are the symptoms of Raynaud's phenomenon?
Other symptoms and signs may include: Change of the color of hands and/or feet (from normal to white to a purplish-blue color) with cold, called " Raynaud's Phenomenon ," but Raynaud's is very common in persons without cryoglobulinemia. Weight loss. High blood pressure. Swelling of ankles and legs.
How to tell if you have Raynaud's?
Other symptoms and signs may include: 1 Change of the color of hands and/or feet (from normal to white to a purplish-blue color) with cold, called " Raynaud's Phenomenon ," but Raynaud's is very common in persons without cryoglobulinemia. 2 Weight loss 3 High blood pressure 4 Swelling of ankles and legs 5 Skin ulcers and gangrene 6 Enlarged liver or spleen 7 Numbness, tingling or weakness of hands or feet 8 Kidney damage
Is cryoglobulinemia always necessary?
Treatment of cryoglobulinemia is not always necessary and depends on the organs affected, degree of damage, and presence of other medical conditions. It is very important not only to treat the cryoglobulinemia but also to address any other associated disorders.
Can a cryoglobulinemia be idiopathic?
Cryoglobulinemia can be present alone ("idiopathic") or can be associated with other diseases such as: Infection, particularly hepatitis C infection. Blood cell abnormalities such as lymphoma and multiple myeloma. Connective tissue disease such as lupus.
What is the cause of cryoglobulinemia?
Cryoglobulinemia is a disease caused by an abundance of a protein called cryoglobulin in the blood. Cryoglobulins are proteins found in the blood stream that clump together in colder temperatures. These clusters cause blood plasma to become very thick, which can block normal blood flow to tissue and organs. Cryoglobulinemia is most common in adults ...
How many types of cryoglobulinemia are there?
There are four main types of cryoglobulinemia:
What causes clumps of abnormal proteins in the blood stream that can block blood flow?
Cryoglobulinemia causes clumps of abnormal proteins in the blood stream that can block blood flow. The blockages can, in turn, cause tissue, joint, nerve, and organ damage. The causes of cryoglobulinemia vary from person to person. Some of the most common causes include: having an abundance of cryoglobulin in the blood. certain blood cell cancers.
What is the purpose of determining the type of cryoglobulins present?
Determining the type of cryoglobulins present will help a doctor determine how best to treat the disease. The type may also help the doctor identify what underlying condition or disease is causing the cryoglobulinemia.
What is the treatment for secondary cryoglobulinemia?
In cases of secondary cryoglobulinemia, treatment involves correcting the underlying condition. When the underlying cause is treated, the symptoms of cryoglobulinemia should improve as well.
Is essential cryoglobulinemia a disease?
Essential cryoglobulinemia has no association with a disease or underlying condition. The presence of type 2 and 3 cryoglobulinemia and their association with hepatitis C lead some researchers to believe there may not be such thing as essential cryoglobulinemia.
Can cryoglobulinemia flare in the summer?
Some people experience continuous symptoms while others go through periods of flares. As cold temperatures play a role in cryoglobulinemia, people may experience flares during colder months and fewer symptoms in the summer.
What are the symptoms of cryoglobulinemia?
Common symptoms include skin lesions, joint pain (arthralgia), arthritis, vascular purpura (purple skin marks), livedo (marbling pattern), bleeding conditions and weakness, but specific symptoms can vary greatly from one person to another and can potentially involve multiple organ systems. The severity of cryoglobulinemia is highly variable. Skin, joints, and nerves are commonly affected. Kidney disease is somewhat less common and with a wide range of severity. The heart, brain, or gastrointestinal tract each are affected in fewer than 10% of cases.
How many people have cryoglobulinemia?
Cryoglobulinemia tends to develop between 40-60 years of age and affect females more than males by 3:1. Cryoglobulinemia is estimated to affect 1 in 100,000 individuals. Essential mixed cryoglobulinemia occurs in about 1 in 100,000 people.
Why should cryoglobulinemia patients avoid cold environments?
Patients with cryoglobulinemia should be advised to avoid cold environments to prevent triggering the precipitation of cryoglobulins.
What are the different types of cryoglobulins?
Type I cryoglobulinemia is usually associated with an underlying disorder, specifically certain types of cancer. Type II and type III cryoglobulinemia are known as mixed cryoglobulinemia. In these disorders, cryoglobulins are abnormal immune complexes. An immune complex is formed when an antibody attaches to an antigen. Unlike type I cryoglobulinemia, the cryoglobulins in type II and type III contain rheumatoid factor, which is an autoantibody (i.e. an antibody that attacks the body own tissue). The distinction between type II and type III cryoglobulinemia is mostly technical and deals with whether the rheumatoid factor is monoclonal or polyclonal. The clinical pictures of type II and III cryoglobulinemia are similar.
What causes numbness in the tips of the fingers?
Peripheral neuropathy. Cryoglobulinemia can damage the nerves at the tips of your fingers and toes, causing numbness and other problems.
How does cold agglutinin disease differ from cryoglobulinemia?
In cold agglutinin disease, antibodies (different from those in cryoglobulinemia) attack and kill red blood cells, which then accumulate and block blood vessels 2).
What is the treatment for severe cryoglobulinemia?
Severe cryoglobulinemia involves vital organs or large areas of skin. It is treated with corticosteroids and other medicines that suppress the immune system.
What is Cryoglobulinemia?
Cryoglobulins are unusual proteins in the blood. These proteins might clump together at temperatures below 98.6 F (37 C) if you have cryoglobulinemia. These gelatinous protein clumps could impede your blood circulation, which could damage your skin, joints, nerves, and organs especially your kidneys and liver.
Cryoglobulinemia Symptoms
Skin lesions - Most people who have cryoglobulinemia develop purplish skin lesions on their legs. In some people, leg ulcers also happen.
Cryoglobulinemia Diagnosis
Diagnosis of cryoglobulinemia involves a blood test in which the sample should be kept at normal body temperature, 98.6 F (37 C), for a period of time before being cooled. Inaccurate test results could happen if the blood sample is not handled properly.
Cryoglobulinemia Treatment
Depending on the hidden cause of cryoglobulinemia, treatment might include medications that suppress the immune system or fight viral infections.
How to diagnose cryoglobulinemia?
In diagnosing cryoglobulinemia, your doctor will consider a number of factors, including a detailed medical history; physical examination; laboratory tests; specialized imaging studies; and, when indicated, a biopsy of an affected tissue or organ. A specific blood test to detect the presence and type of cryoglobulins in the blood will likely be ordered. These results can help determine how best to treat the disease and identify the underlying disease or cause of the condition. All patients with cryoglobulinemia should be tested for HCV.
What is the treatment for cryoglobulinemia?
Cryoglobulinemia is commonly treated with corticosteroids such as prednisone, and medications that suppress the immune system. Antiviral drugs are prescribed when HCV is present. Left untreated, the disease can cause permanent tissue and organ damage, so it is important to seek prompt medical care when symptoms appear.
What is the name of the disease that causes blood vessels to clump together?
Cryoglobulinemia is a form of vasculitis—a family of rare disorders characterized by inflammation of the blood vessels, which can restrict blood flow and damage vital organs and tissues. In cryoglobulinemia , abnormal blood proteins called cryoglobulins clump together at cold temperatures, restricting blood flow and causing damage to skin, muscles, nerves, and organs—especially the kidneys. More rarely, it can affect the heart, brain, and gastrointestinal tract. Cryoglobulinemia almost always occurs in people who have hepatitis C virus (HCV).
What kind of doctor treats cryoglobulinemia?
In addition to a primary care provider, you may need to see the following specialists: rheumatologist (joints, muscles, immune system); dermatologist (skin); hematologist (blood disorders); nephrologist (kidney disease); hepatologist (liver); cardiologist (heart); neurologist (brain/nervous system); or others as needed.
What tests are used to diagnose cryoglobulinemia?
In diagnosing cryoglobulinemia, your doctor will consider a number of factors, including a detailed medical history; physical examination; laboratory tests; specialized imaging studies; and, when indicated, a biopsy of an affected tissue or organ.
Does cryoglobulinemia affect the heart?
More rarely, it can affect the heart, brain, and gastrointestinal tract. Cryoglobulinemia almost always occurs in people who have hepatitis C virus (HCV). People with cryoglobulinemia may or may not have symptoms.
Can cryoglobulinemia be detected in blood?
The symptoms of cryoglobulinemia vary depending on the organ systems affected. Some people may have no signs except for elevated cryoglobulin levels detected in a blood test. However, when symptoms are present, they typically include the following:
How to treat cryoglobulinemia?
Treatment depends on the type of cryoglobulin, underlying disease, and severity of symptoms. Cryoglobulinemia with severe hyperviscosity syndrome requires plasmapheresis and chemotherapy of the underlying malignancy. Some patients with cryoglobulinemia suffer from mild, recurrent crops of lower extremity purpura that require no specific therapy. More extensive vasculitis associated with autoimmune diseases or essential cryoglobulinemia may respond to prednisone, cyclophosphamide, or both. The most effective treatment for cryoglobulinemia associated with hepatitis C has not yet been determined. Brief use of prednisone followed by 6 months of interferon alfa has produced clinical and liver function test improvement, but relapse of liver disease and vasculitis often occurs when interferon alfa is stopped.
Who wrote the book Cryoglobulinemia?
In medical terms, by David Hellmann, M.D. A discussion of Cryoglobulinemia written in medical terms by David Hellmann, M.D. (F.A.C.P.), Co-Director of the Johns Hopkins Vasculitis Center, for the Rheumatology Section of the Medical Knowledge Self-Assessment Program published and copyrighted by the American College of Physicians (Edition 11, 1998).
What is the name of the disease that causes antibodies to precipitate under cold conditions?
Cryoglobulinemia. The name literally means “cold antibody in the blood”, which refers to the chemical properties of the antibodies that cause this disease: cryoglobulins are antibodies that precipitate under cold conditions. Drug use is a prime risk factor for cryoglobulinemia because more than 90% of cases of cryoglobulinemic vasculitis are ...
Does cryoglobulinemia remit hepatitis C?
It is now evident that most patients diagnosed with type II or type III mixed essential cryoglobulinemia have the disease as an immune response to chronic hepatitis C infection. The role of hepatitis C virus is suggested by finding that the cryoglobulins in these patients are enriched with anti–hepatitis C antibody and hepatitis C RNA. Moreover, antviral therapy can remit the disease in some patients.
What are the clinical features of cryoglobulinemic disease?
The clinical features of cryoglobulinemic disease can reflect those due not only to the circulation of cryoglobulins but also to any underlying hematological premalignant or malignant disorder, infectious disease, or autoimmune syndrome. The following sections of clinical features focuses on those attributed to the cryoglobulins. Cryoglobulins cause tissue damage by three mechanisms; they can: 1 a) increase blood viscosity thereby reducing blood flow to tissues to cause the hyperviscosity syndrome (i.e., headache, confusion, blurry or loss of vision, hearing loss, and epistaxis; 2 b) deposit in small arteries and capillaries thereby plugging these blood vessels and causing infarction and necrosis of tissues including in particular skin (e.g., ears), distal extremities, and kidneys; 3 c) in type II and type III disease, deposit on the endothelium of blood vessels and activate the blood complement system to form pro-inflammatory elements such as C5a thereby initiating the systemic vascular inflammatory reaction termed cryoglobulinemic vasculitis.
What is cryoglobulinemia?
in 1967, the percentage of cryoglobulinemic diseases described as essential cryoglobulinemia or idiopathic cryoglobulinemia, that is cryoglobulinemic disease that is unassociated with an underlying disorder, has fallen. Currently most cases of this disease are found to be associated with premalignant, malignant, infectious, or autoimmune disorders that are the known or presumed causes for the production of cryoglobulins. This form of non-essential or non-idiopathic cryoglobulinemic disease is classically grouped into three types according to the Brouet classification. The classification distinguishes three subtypes of cryoglobulinemic diseases based on two factors, the class of immunoglobulins in the cryoglobulin and the association of the cryoglobulinemic disease with other disorder. The following table lists these three types of cryoglobulinemic disease, characterized on the monoclonal immunoglobulin (s) comprising the involved cryoglobulin, percentage of total cryoglobulinemic disease cases, and class of disorders associated for each type.
What are the symptoms of type II and III?
Types II and III (or mixed or variant) cryoglobulinemic disease may also present with symptoms and signs of blood hyperviscosity syndrome and deposition of cryoglobulins within blood vessels but also include those attributable to cryo globulinemic vasculitis.
What is type 1 cryoglobulinemic disease?
Type I cryoglobulinemic disease. Signs and symptoms due to the cryoglobulins of type I disease reflect the hyperviscosity and deposition of cryoglobulins within the blood vessels which reduce or stop blood perfusion to tissues. These events occur particularly in cases where blood cryoglobulin levels of monoclonal IgM are high in patients ...
What are monoclonal IgM proteins?
The monoclonal or polyclonal IgM proteins involved in Types II and III cryoglobulinemic disease have rheumatoid factor activity. That is, they bind to polyclonal immunoglobulins, activate the blood complement system, and thereby form tissue deposits that contain IgM, IgG (or, rarely, IgA), and components of the complement system, including in particular complement component 4. The vascular deposition of these types of cryoglobulin-containing immune complexes and complement can cause a clinical syndrome of cutaneous small-vessel vasculitis characterized by systemic vasculitis and inflammation termed cryoglobulinemic vasculitis. Accordingly, type II and type III cryoglobulinemic diseases are often grouped together and referred to as mixed cryoglobulinemia or mixed cryoglobulinemic disease. The monoclonal IgM involved in Type I cryoglobulinemic diseases lacks rheumatoid factor activity.
What is the name of the condition where the body contains antibodies that become insoluble at low temperatures?
Cryoglobulinemia is a medical condition in which the blood contains large amounts of pathological cold sensitive antibodies called cryoglobulins – proteins (mostly immunoglobulins themselves) that become insoluble at reduced temperatures. This should be contrasted with cold agglutinins, which cause agglutination of red blood cells .
What temperature does agglutination occur?
Cryoglobulins typically precipitate (clumps together) at temperatures below normal body temperature – 37 degrees Celsius (99 degrees Fahrenheit) – and will dissolve again if the blood is heated.
What is the name of the disease that causes cryoglobulinemia?
Cryoglobulinemia can be associated with a kidney (renal) disease known as membranoproliferative glomerulonephritis (MPGN) type I characterized by a specific pattern of injury to the kidney most likely caused by deposition of cryoglobulins in the kidney. MPGN type I can be a severe complication, eventually leading to kidney failure.
What is mixed cryoglobulinemia?
Mixed cryoglobulinemia is believed to be an immune-mediated disorder (in which the immune system response to chronic infection causes damage to various tissues) or an autoimmune disorder (in which the immune system mistakenly attacks the body’s own tissue).
What tests can be performed to detect hepatitis C?
Additional tests may be performed to detect underlying disorders potentially associated with cryoglobulinemia such as liver function tests that can reveal hepatitis C virus infection.
How long does cryoglobulinemia stay in the cell?
The sample may be required to be stored for 5-7 days. Eventually, the sample will be spun down in the centrifuge to separate out the cells. If cryoglobulinemia is present, this will cause a white precipitate to form that redissolves upon rewarming.
What is type II and type III cryoglobulinemia?
Type II and type III cryoglobulinemia are known as mixed cryoglobulinemia. In these disorders, cryoglobulins are abnormal immune complexes. An immune complex is formed when an antibody attaches to an antigen. Unlike type I cryoglobulinemia, the cryoglobulins in type II and type III contain rheumatoid factor, which is an autoantibody (i.e.
What is the function of the immune system in cryoglobulinemia?
The immune system is divided into several components, the combined actions of which are responsible for defending against infectious agents. The T cell system (cell-mediated immune response) contributes to fighting several viruses, some bacteria and yeast and fungi. The B cell system (humoral immune response) fights infection caused by other viruses and bacteria. It does so by secreting immune factors called antibodies (also known as immunoglobulins) into the fluid portion of the blood (serum) and body secretions (e.g. saliva). There are five classes of immunoglobulins (Ig) known as IgA, IgD, IgE, IgG, and IgM. Antibodies can directly kill microorganisms or coat them so they are more easily destroyed by white blood cells. Any substance that triggers a response by the immune system is known as an antigen. Cryoglobulinemia is generally broken down in three subtypes. In type I cryoglobulinemia, cryoglobulins are made up of a specific immunoglobulin, usually IgM. Type I cryoglobulinemia is usually associated with an underlying disorder, specifically certain types of cancer. Type II and type III cryoglobulinemia are known as mixed cryoglobulinemia. In these disorders, cryoglobulins are abnormal immune complexes. An immune complex is formed when an antibody attaches to an antigen. Unlike type I cryoglobulinemia, the cryoglobulins in type II and type III contain rheumatoid factor, which is an autoantibody (i.e. an antibody that attacks the body own tissue). The distinction between type II and type III cryoglobulinemia is mostly technical and deals with whether the rheumatoid factor is monoclonal or polyclonal. The clinical pictures of type II and III cryoglobulinemia are similar. This report primarily deals with mixed cryoglobulinemia.
How many people have mixed cryoglobulinemia?
Mixed cryoglobulinemia affects approximately 30%-50% of individuals with chronic hepatitis C infection. However, only 10%-30% of those individuals actually develop symptoms of mixed cryoglobulinemia ...
