Cryoglobulinemia is a disease belonging to the group of vascular inflammations (vasculitides). In most cases, chronic hepatitis C underlies the inflammation.
What is cryoglobulinemia?
Cryoglobulinemia is a vasculitis, or inflammation of the blood vessels. This inflammation is triggered by the deposition of immune complexes or immunoglobulins in the small blood vessels. These immunoglobulins are called cryoglobulins. When cold, they are insoluble. However, in warm conditions, 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).
- Type 2 cryoglobulins are mostly monoclonal immunoglobulin M. This binds to a specific piece of IgG. Thus, mixed cryoglobulins are present here.
- Type 3 cryoglobulins are polyclonal immunoglobulins M. Together with other polyclonal immunoglobulins, type 3 cryoglobulins form immune complexes.
Causes
Cryoglobulins lose their ability to dissolve in cold temperatures. They deposit in the small blood vessels and cause inflammation there. Usually, cryoglobulinemia is a sequelae of diseases in which significantly more immunoglobulins are present than in a healthy state. In 80 percent of all cases, chronic hepatitis C underlies cryoglubulinemia. Other possible triggering diseases are Sjögren’s syndrome, Lyme disease, rheumatoid arthritis, subacute bacterial endocarditis, syphilis, toxoplasmosis or multiple myeloma. Infection with Epstein-Barr virus, the causative agent of glandular fever, can also result in cryoglobulinemia.
Symptoms, complaints, and signs
The inflammation causes damage to the vessel walls. This vascular wall damage occurs particularly on the hands, feet, nose, ears, chin, penis, and vulva. Here, skin hemorrhages known as palpable purpura are seen. In addition, acrocyanosis or necrosis of the acras occurs. Acrocyanosis is a blue discoloration of the acra. Acras are the parts of the body farthest from the trunk. A typical manifestation of cryoglobulinemia is Raynaud’s syndrome. The disease is also known as Raynaud’s disease and is characterized by intermittent paling of the fingers. This paling is due to spasmodic constriction of the inflamed blood vessels. In addition, joint and muscle pain may occur. Patients also complain of neurological manifestations such as tingling or formication. Liver enlargement is found in more than half of patients. The spleen may also be enlarged. Splenomegaly and liver enlargement are typical of cryoglobulinemia underlying Waldenström’s disease or plasmacytoma. Furthermore, lymph node disease may occur. In some cases, glomerulonephritis develops. Here, the renal corpuscles are inflamed. As a result, blood (hematuria) and proteins (proteinuria) are found in the urine. In severe forms, multiple organ infarctions can occur. Renal infarction, stroke, myocardial infarction, or mesenteric infarction are acutely life-threatening.
Diagnosis and course of the disease
Initial evidence of cryoglobulinemia is provided by the medical history. Evidence of chronic hepatitis C may be present. At a temperature of 37 degrees Celsius, the erythrocyte sedimentation rate is greatly increased, whereas at a temperature of four degrees Celsius, it is normal. Cryoglobulins circulating in the blood can be detected by the electrophoresis method. In electrophoresis, serum proteins are separated and displayed in their individual fractions. In cryoglobulinemia, γ-globulins are increased in the blood. The diagnosis can be confirmed with a vascular biopsy. Here, a piece of vessel is taken. Based on this piece of vessel, the inflammation can be detected.
Complications
Cryoglobulinemia usually causes damage to the vessel walls. This mainly involves skin bleeding, which may be associated with pain. Furthermore, the disease also causes the skin to turn blue and swelling may occur in the affected areas.It is not uncommon for movement restrictions to occur on the body, which can significantly complicate the patient’s everyday life. Pain in the muscles and joints is also not uncommon in cryoglobulinemia and can significantly reduce the patient’s quality of life. Furthermore, the disease also causes the liver to become enlarged. In the worst case, diseases of the liver can lead to the death of the patient. Not infrequently, the heart is also affected by the disease, so that a heart attack can still occur. Kidney infarction is also not ruled out in cryoglobulinemia. The life expectancy of the patient is considerably reduced and limited by cryoglobulinemia. Treatment of this disease takes place with the help of medications. Complications do not occur in this process. The symptoms can be treated with the help of ibuprofen. Whether there is a reduction in life expectancy usually cannot be universally predicted.
When should you see a doctor?
Skin discoloration in various parts of the body is cause for concern. If blue discoloration occurs repeatedly or if there is an increase in discoloration, a doctor should be consulted for clarification of symptoms. The hands, feet, ears, nose and chin are particularly at risk. The cause of the skin abnormalities should be investigated and treated by a physician. In some cases, the blue discoloration occurs in the area of the reproductive organs. Therefore, a visit to the doctor is also necessary if the penis or vulva show changes. If there is a sudden paling of the fingers that cannot be explained, a doctor should be informed of the observations. A doctor is needed if there are sensory disturbances on the skin, a tingling sensation, or numbness. If joint pain or muscular system discomfort occurs, a physician should be consulted. This is especially true if there has been no physical overexertion or intense athletic activity. If there is a feeling of tightness in the upper body, circulatory problems or irregularities in the heart rhythm, a doctor should be consulted. If the symptoms persist over a longer period of time, a life-threatening condition may develop. Therefore, a visit to the doctor should be made at the first signs. In the event of a functional failure or loss of consciousness, an emergency physician should be called. In addition, taking first aid measures is necessary to ensure the survival of the affected person.
Treatment and therapy
The basis of therapy is treatment of the underlying disease. In chronic hepatitis C, this is not an easy undertaking. Affected individuals receive a combination of interferon-α and the antiviral drug ribavirin for a period of at least six months. However, the therapy works poorly if the viral load is high and the infection is of different subtypes. Overall, the success rate is 50 percent. Accompanying treatment of the underlying disease, corticosteroids are used in high doses. Chemotherapeutic agents and interferons are also used. The standard dosage consists of cyclophosphamide, prednisolone and ibuprofen. However, ibuprofen is used exclusively for symptomatic treatment.
Outlook and prognosis
The prognosis of cryoglobulinemia depends on the underlying disease present. The treatment option of the triggering disease is crucial 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 patient has hepatitis C, the treatment plan and the prospects of recovery are particularly difficult and protracted. The probability of achieving freedom from symptoms is only about half of the cases diagnosed. In addition, side effects and risks can occur within an initiated therapy. Without medical and medical treatment, the prognosis for the affected person deteriorates immensely. Consequential diseases are possible and, in addition, there is a risk of serious complications. Some patients are diagnosed with renal infarction. This is potentially life-threatening for the affected person and can lead to lifelong impairments if intensive medical care is successful. In addition, the overall average life expectancy in these patients is reduced.If the treating physician succeeds in curing the underlying disease at hand, the symptoms of cryoglobulinemia gradually disappear on their own. Despite an achieved cure, a relapse of the disease may occur in the course of life. The organism does not develop immunity over the germs causing the disease. Therefore, special precautions should be taken to maintain long-term freedom from symptoms.
Prevention
In principle, cryoglobulinemia can be prevented only by prevention of the underlying disease. Hepatitis C is a major risk factor for the development of cryoglobulinemia. Liver inflammation caused by the hepatitis C virus shows a very high rate of chronicity and can also cause liver damage. The disease is transmitted via 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. For the prevention of hepatitis C and thus also for the prevention of cryoglobulinemia, tattoo and piercing studios should be closely inspected before the actual piercing appointment. Hygienic work should be a matter of course. Drug addicts should not share injecting equipment with other users, but should always use sterile disposable syringes. Despite the low risk of transmission, only protected intercourse should be practiced with regard to other STDs. In the case of known diseases associated with increased production of immunoglobulins, those affected should look out for symptoms such as cold and pale hands or bleeding. If vasculitis is suspected, a physician should be consulted immediately. Early treatment improves prognosis and prevents permanent damage, such as neuropathy and muscle pain.
Follow-up
In most cases, the options for follow-up care in cryoglobulinemia are severely limited, and in some cases they are not available to the affected person at all. In this regard, the further course of the disease is very much dependent on the condition of the affected person and also on the time of diagnosis, so no general prediction can be made about this. However, an early diagnosis of the disease usually always has a positive effect on the further course of cryoglobulinemia, so that the affected person should ideally see a doctor at the first signs and symptoms. As a rule, the disease cannot be cured on its own. Those affected are dependent on taking various medications. These usually have to be taken over a period of six months, and care must always be taken to ensure that they are taken regularly and in the correct dosage. Furthermore, regular checks and examinations should be carried out by a doctor so that the condition of the affected person is permanently monitored. In most cases, cryoglobulinemia can be defeated relatively well, so that no further follow-up measures are necessary.
What you can do yourself
In cases of cryoglobulinemia, self-help measures are usually limited to supporting medical treatment of symptoms and making everyday life with the disease easier. Initially, a change in lifestyle habits is indicated. Since cryoglobulinemia is mostly due to bacterial diseases, the immune system must be strengthened. This can be achieved by the patient taking plenty of exercise in the fresh air and eating a healthy diet. In addition, care should be taken to ensure a restful night’s sleep and to avoid stress. If the complaints are based on a serious illness that is not only caused by a bacterial pathogen, symptomatic concomitant treatment is possible. Pain, for example, can be alleviated by a number of natural remedies. The preparations Belladonna D12 from homeopathy as well as Arnica and Devil’s Claw from naturopathy have proven to be effective. Conservative measures such as warm compresses also help with local pain. Depending on the underlying disease of cryoglobulinemia, further measures may be taken under certain circumstances. However, this should be discussed with a doctor beforehand to avoid discomfort and serious complications.
