Cryoglobulinemia is a condition in which there is a large amount of abnormal proteins called cryoglobulins in the blood. What are the causes and symptoms of cryoglobulemia? How is this systemic disease treated?

Cryoglobulinemia(Latincryoglobulinemia ) may appear spontaneously, mainly in middle-aged women, but it most often accompanies many chronic diseases and may manifest as numerous organ complications.

Cryoglobulins are antibodies that may occur in small amounts in he althy people, and the symptoms of the disease usually appear when their concentration exceeds about 100 mg / liter. In mild cryoglobulinemia, the antibodies precipitate at temperatures lower than 4oC. The higher the cryoglobulin concentration, the higher the temperature the precipitation occurs. The process is fully reversible; precipitated proteins dissolve in the blood when the temperature reaches a value greater than 37oC.

Classification of cryoglobulinemia

The classification of cryoglobulinemia developed by Bruet in 1974 is still valid. It is based on the composition of the cryoglobulins found in the blood. Therefore, we can distinguish:

  • Type I - monoclonal cryoglobulinemia in which mainly IgM immunoglobulins occur. It is assigned to various types of proliferative diseases, such as multiple myeloma, Waldenström's macroglobulinemia, chronic lymphocytic leukemia and non-Hodgkin's lymphoma.
  • Type II - mixed monoclonal-polyclonal cryoglobulinemia, characterized by the presence of rheumatoid factor (it is a protein that is present in the blood in many cases as a marker of autoimmune diseases). It is accompanied by lymphoproliferative diseases, autoimmune diseases and, above all, HCV infection.
  • Type III - mixed polyclonal cryoglobulinemia, in which several classes of immunoglobulins are detected and, as in type II, rheumatoid factor. It is most often associated with viral infections such as HCV, HBV, CMV, EBV, and with autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis.

Cryoglobulinemia can also be classified according to the clinical classification, which is distinguished by:

  • Essential cryoglobulinemia, so-called idiopathic, which is not related tothe presence of other diseases;
  • secondary cryoglobulinemia, which is associated with various disease states, such as autoimmune, infectious, and lymphoproliferative diseases. Cryoglobulinemia may also occur in the course of certain liver diseases.

Pathophysiology of cryoglobulinemia

The mechanisms of the formation of cryoglobulinemia have not been fully understood until today. It is known that temperature fluctuations are accompanied by changes in the structure of immunoglobulins, which in turn result in a change in their solubility. Precipitation immune complexes are difficult to remove from the circulation, build up in tissues and vessels, and can cause diseases such as chronic vasculitis or glomerulonephritis. In addition, the precipitation of cryoglobulins leads to thrombosis and blockage of small vessels, which leads to ischemia and necrosis of the peripheral parts of the limbs or to acute renal failure. The very presence of a large amount of cryoglobulins leads to an increase in blood viscosity, which predisposes to vascular complications.

Symptoms of cryoglobulinemia

Cryoglobulinemia can manifest itself in different ways, and it largely depends on its type.

Characteristic for cryoglobulinemia is the so-called Meltzer triad, which consists of vascular purpura, general weakness and joint pain.

The first type is closely related to blood thinning and thrombosis, therefore the symptoms will include such conditions as:

  • acrocyanosis (permanent, painless reddening of the fingers)
  • arterial thrombosis
  • Raynaud's syndrome
  • hemorrhagic diathesis
  • mesh cyanosis
  • necrosis of the subcutaneous tissue

Due to the fact that type II and III cryoglobulinemia have many features in common, the symptoms are very similar. Some of the disease syndromes that can be found here include, among others: joint involvement with painfulness, fatigue, muscle pain, renal manifestation of immune complex disease, and peripheral neuropathy. In addition, there may be skin lesions located mainly on the lower extremities, such as erythematous spots, hemorrhagic papules or even ulcerations. Liver or kidney dysfunction may also appear here.

Diagnostics of cryoglobulinemia

Cryoglobulins are detected in detailed analysis of a blood sample using various immunoassays. The rheumatoid factor in high titres is present in the second and third types of cryoglobulinemia. Cryoglobulinemia is also characterized by a decrease in the concentration of the C4 componentgenitive.

Cryoglobulinemia: treatment

Sometimes cryoglobulinemia is asymptomatic, then treatment is not necessary. In other cases, supportive treatment consists in avoiding low temperatures and in the cold season wearing appropriate clothes that protect primarily the distal parts of the limbs.

In the presence of HCV infection, antiviral treatment should be introduced, which mainly includes interferon and ribavirin. Immunosuppressive therapy is based on the use of interferon, cyclosporin, cytotoxic drugs, glucocorticosteroids, colchicine, monoclonal antibodies and intravenous administration of immunoglobulins, among others.

The only method that can significantly lower the concentration of cryoglobulins in the blood is plasmapheresis. If there is a systemic inflammatory process, it is recommended to use non-steroidal anti-inflammatory drugs, glucocorticosteroids and colchicine.

Category:

Cardiology