Cryoglobulinemia 101

Cryoglobulinemia is a disease from the group of vascular inflammations (vasculitis). In most cases, the inflammation is due to chronic hepatitis C.

What is cryoglobulinemia?

Chronic hepatitis C is the underlying cause of cryoglubulinemia in 80 percent of all cases. See AbbreviationFinder for abbreviations related to Cryoglobulinemia.

Cryoglobulinemia is vasculitis, i.e. inflammation of the blood vessels. This inflammation is triggered by the deposit of immune complexes or immunoglobulins in the small blood vessels. These immunoglobulins are called cryoglobulins. They are insoluble when cold. With heat, however, they can go into solution. Mixed cryoglobulins are also called immune complexes.

Three different types of cryoglobulins can be distinguished:

  • Type 1 cryoglobulins are usually monoclonal immunoglobulins G (IgG) or monoclonal immunoglobulins M (IgM).
  • The type 2 cryoglobulins are usually the monoclonal immunoglobulin M. This binds to a special part of the IgG. Mixed cryoglobulins are present here.
  • Type 3 cryoglobulins are polyclonal immunoglobulins M. Together with other polyclonal immunoglobulins, type 3 cryoglobulins form immune complexes.


In the cold, cryoglobulins lose their ability to dissolve. They are deposited in the small blood vessels and cause inflammation there. As a rule, cryoglobulinemia is a consequence of diseases in which significantly more immunoglobulins are present than in a healthy state. Chronic hepatitis C is the underlying cause of cryoglubulinemia in 80 percent of all cases.

Other possible triggering diseases are Sjögren’s syndrome, Lyme disease, rheumatoid arthritis, subacute bacterial endocarditis, syphilis, toxoplasmosis or multiple myeloma. Infection with the Epstein-Barr virus, the causative agent of glandular fever, can also result in cryoglobulinemia.

Symptoms, Ailments & Signs

The walls of the blood vessels are damaged by the inflammation. This damage to the vascular wall occurs in particular on the hands, feet, nose, ears, chin, penis and vulva. This is where skin bleeding occurs, which is referred to as palpable purpura. In addition, there is acrocyanosis or necrosis of the acral. Acrocyanosis is a blue discoloration of the acral bones.

Acres are the parts of the body furthest from the torso. A typical manifestation of cryoglobulinemia is Raynaud’s syndrome. The disease is also known as Raynaud’s disease and is characterized by paroxysmal paling of the fingers. This paling is due to a spasmodic constriction of the inflamed blood vessels. Joint and muscle pain can also occur. Patients also complain of neurological symptoms such as tingling or pins and needles.

Liver enlargement is found in more than half of the patients. The spleen can also be enlarged. Enlarged spleen and liver are typical of cryoglobulinemia caused by Waldenstrom’s disease or plasmacytoma. Lymph node diseases can also occur. In some cases, glomerulonephritis develops .

Here the kidney corpuscles are inflamed. This leads to blood (hematuria) and proteins (proteinuria) in the urine. In severe cases, multiple organ infarctions can occur. Renal infarction, stroke, heart attack or mesenteric infarction are acutely life-threatening.

Diagnosis & course of disease

The medical history provides the first indications of cryoglobulinemia. There may be evidence of chronic hepatitis C. At a temperature of 37 degrees Celsius, the blood sedimentation rate is greatly increased, at a temperature of four degrees Celsius, on the other hand, it is normal. The cryoglobulins circulating in the blood can be detected using the electrophoresis method.

During electrophoresis, the serum proteins are separated and presented in their individual fractions. In the case of cryoglobulinemia, the γ-globulins are found in increased amounts in the blood. The diagnosis can be confirmed with a vascular biopsy. Here a piece of vessel is removed. The inflammation can be detected on the basis of this piece of vessel.


Cryoglobulinemia usually causes damage to the vessel walls. This is where skin bleeding occurs, which can be associated with pain. The disease also turns the skin blue and swelling can occur in the affected areas. It is not uncommon for there to be restricted movement in the body, which can make the patient’s everyday life significantly more difficult.

Pain in the muscles and joints is also not uncommon in cryoglobulinemia and can significantly reduce the patient’s quality of life. The disease also enlarges the liver. In the worst case, diseases of the liver can lead to the death of the patient. It is not uncommon for the heart to be affected by the disease, so that a heart attack can still occur.

A renal infarction cannot be ruled out in the case of cryoglobulinemia. The patient’s life expectancy is significantly reduced and restricted by cryoglobulinemia. Treatment of this disease takes place with the help of drugs. There are no complications. The symptoms can be treated with the help of ibuprofen. As a rule, it cannot be universally predicted whether there will be a reduction in life expectancy.

When should you go to the doctor?

Skin discoloration on different parts of the body is a cause for concern. If blue discolouration occurs repeatedly or if the discolouration increases, a doctor should be consulted to clarify the symptoms. The hands, feet, ears, nose and chin are particularly at risk. The cause of the skin abnormalities should be examined and treated by a doctor. In some cases, the blue discoloration occurs in the genital area. Therefore, a doctor’s visit is also required if the penis or vulva show changes.

If there is an unexplained sudden paleness of the fingers, a doctor should be informed of the observations. A doctor is required in the event of sensory disturbances on the skin, a tingling sensation or numbness. If you experience joint pain or muscle problems, consult a doctor. This applies in particular if no physical exertion or intensive sporting activities have taken place. If you feel tight in your upper body, have circulatory problems or have an irregular heart rhythm, you should consult a doctor.

If the symptoms persist for a long time, a life-threatening condition can develop. Therefore, a doctor’s visit should be made at the first sign. In the event of a functional failure or loss of consciousness, an ambulance must be called. In addition, it is necessary to take first aid measures to ensure the survival of the person concerned.

Treatment & Therapy

The basis of therapy is the treatment of the underlying disease. With chronic hepatitis C, this is no easy task. Those affected receive a combination of interferon-α and the antiviral ribavirin over a period of at least six months. With a high viral load and infection with different subtypes, however, the therapy only works poorly. Overall, the success rate is 50 percent.

Corticosteroids are used in high doses to accompany the treatment of the underlying disease. Chemotherapy drugs and interferons are also used. The standard dosage consists of cyclophosphamide, prednisolone, and ibuprofen. However, ibuprofen is only used for symptomatic treatment.

Outlook & Forecast

The prognosis of cryoglobulinemia depends on the underlying disease. The treatment option for the triggering disease is decisive for the further course of the disease and the prospect of recovery. In addition, it is of particular importance whether the present disease has a chronic character. For example, if the person affected is suffering from hepatitis C, the treatment plan and the chances of recovery are particularly difficult and lengthy. The probability of achieving freedom from symptoms is only about half of the diagnosed cases. In addition, side effects and risks can occur within an initiated therapy.

Without medical and medical treatment, the prognosis for those affected deteriorates immensely. Secondary diseases are possible and there is also a risk of serious complications. Renal infarction is detected in some patients. This is potentially life-threatening for those affected and can lead to life-long impairments if intensive medical care is successful. In addition, the average life expectancy in these patients decreased overall.

If the doctor treating you succeeds in curing the underlying disease, the symptoms of cryoglobulinemia will gradually disappear on their own. Despite an achieved cure, a recurrence can occur in the course of life. The organism does not develop immunity to the disease-causing germs. Therefore, special precautions should be taken to maintain long-term freedom from symptoms.


In principle, cryoglobulinemia can only be prevented by preventing the underlying disease. Hepatitis C is a major risk factor for developing cryoglobulinemia. Inflammation of the liver caused by the hepatitis C virus shows a very high chronification rate and can also cause liver damage. The disease is transmitted through blood. Vaccination is not yet possible. Intravenous drug use increases the risk of infection.

Hepatitis C can also be transmitted through contaminated instruments in tattoo or piercing studios. Sexual transmission is rather rare. To prevent hepatitis C and thus also to prevent cryoglobulinemia, tattoo and piercing studios should be examined carefully before the actual piercing appointment. Working hygienically should be a matter of course.

Drug addicts should not share injection equipment with other users, but should always use sterile disposable syringes. Despite the low risk of transmission, only protected sex should be practiced, also with regard to other sexually transmitted diseases. In the case of known diseases that are associated with an increased production of immunoglobulins, those affected should watch out for symptoms such as cold and pale hands or bleeding.

If vascular inflammation is suspected, a doctor should be consulted immediately. Early treatment improves the prognosis and prevents permanent damage such as neuropathy and muscle pain.


In most cases, the options for follow-up care for cryoglobulinemia are severely limited, and in some cases they are not available to the person concerned. The further course of the disease depends very much on the condition of the person affected and also on the time of diagnosis, so that no general prediction can be made about it.

However, an early diagnosis of the disease usually always has a positive effect on the further course of cryoglobulinemia, so ideally the person concerned should consult a doctor at the first signs and symptoms. As a rule, this does not lead to an independent healing. Those affected depend on the intake of various medications.

As a rule, these must be taken over a period of six months, whereby it is always important to ensure that they are taken regularly and that the dosage is correct. Furthermore, regular checks and examinations should be carried out by a doctor so that the condition of the person concerned is permanently monitored. In most cases, cryoglobulinemia can be overcome relatively well, so that no further follow-up measures are necessary.

You can do that yourself

In the case of cryoglobulinemia, self-help measures are usually limited to supporting the medical treatment of the symptoms and making everyday life with the disease easier. First of all, a change in lifestyle is indicated. Since cryoglobulinemia is mostly due to bacterial diseases, the immune system must be strengthened. This is achieved by the patient exercising a lot in the fresh air and eating healthily. In addition, care should be taken to ensure a restful night’s sleep and to avoid stress.

If the symptoms are due to a serious illness that was not only triggered by a bacterial pathogen, symptomatic concomitant treatment is possible. Pain can be relieved, for example, by a number of remedies from naturopathy. The preparations Belladonna D12 from homeopathy as well as arnica and devil’s claw from naturopathy have proven themselves . Conservative measures such as warm pads also help with local pain.

Depending on the underlying condition of the cryoglobulinemia, additional measures may be taken. However, this should be discussed with a doctor beforehand to avoid discomfort and serious complications.


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