Overview.
Cryoglobulinemia occurs when the blood contains cryoglobulins. Cryoglobulins are immunoglobulins that tend to form precipitates spontaneously at temperatures below 30°C and dissolve on warming. It excludes a group of serum proteins with similar properties such as cryofibrinogen, C-reactive protein-albumin complexes, and heparin precipitating proteins. Cryoglobulins are classified into three types according to their immunochemical composition: type I is monoclonal to cryoglobulins, and types II and III are mixed cryoglobulins.
Etiology
This pathology is most often secondary to certain primary diseases, such as infections, autoimmune diseases, and certain immunoproliferative disorders.
Symptoms
The clinical manifestations of this disorder are variable, mainly involving the type of cryoglobulin, and may be asymptomatic in some cases, in addition to the clinical manifestations of the primary disease. Other patients often have pathology such as high blood viscosity, red blood cell agglutination, and thrombosis due to cold precipitation of cryoglobulins. Common symptoms include Raynaud’s phenomenon (i.e., cold cyanosis of the extremities), skin purpura, necrosis, ulceration, cold urticaria, arthralgia, and sensory numbness, as well as damage to organs such as the kidneys, brain, liver, and spleen involved in deep vascular involvement.
Examination
1. General laboratory tests
Blood sedimentation often increases, hemoglobin level decreases, thrombocytopenia, blood coagulation disorder, gammaglobulin and gamma globulin increase, rheumatoid factor is often positive with high titer.
2. Immunologic examination
Type I is normal. Complement is often decreased in patients with mixed cryoglobulinemia, especially C4. Immunoglobulin M (lgM) is often increased, and immunoglobulin A (IgG) and immunoglobulin A (IgA) are increased in some patients. Rheumatoid factor, antinuclear antibodies, and cryoglobulin are positive.
3. Measurement of cryoglobulin
More than 90% of patients with type I and more than 80% of patients with type II have cryoglobulin levels >1mg/ml, while more than 80% of patients with type III have levels <1mg/ml.
4. Other
Positive anti-human globulin test (Coombs test), positive antinuclear antibody, direct immunofluorescence showing Ig, complement and fibrinogen deposits in the vessel wall.
Diagnosis
The disease is diagnosed on the basis of clinical manifestations and a significant increase in serum cryoglobulins. It should be noted that cryoglobulin is not easily detected after corticosteroid treatment or after the improvement of pre-existing concomitant diseases, and a temporary increase in cryoglobulin should be excluded.
Differential diagnosis
1. Cryoglobulinemia
It is due to the phenomenon of self-agglutination in small blood vessels after the high efficiency lectin in serum is subjected to cold. The prominent symptoms are cyanosis in limbs, nose and ears, accompanied by numbness and pain, and hemolytic anemia and paroxysmal hemoglobinuria can be seen.
2. Cold fibrinogenemia
The plasma has the protein of condensation, the clinical manifestations are urticaria, limb numbness and hemorrhage, etc. It can be primary or secondary to some malignant diseases.
3. Cyanosis of hands and feet
It is secondary cyanosis due to spasm of fine skin arteries, secondary dilatation of capillaries and veins, mostly without spontaneous symptoms.
Complications
Often accompanied by immunoproliferative diseases, infectious diseases. It often involves skin, kidney and joints, lymph nodes, liver and spleen, and neurological damage.
Treatment
1. General treatment
Treat the primary disease, avoid cold and keep warm. All treatments are temporary and symptomatic.
2. Plasma exchange method
Remove immunoglobulins or immune complexes to rapidly reduce circulating cryoglobulins to relieve cold-induced symptoms.
3. Corticosteroids
Corticosteroids are effective to varying degrees in controlling fever, skin lesions, and arthralgia.
4. Immunosuppressants
Maintain circulating cryoglobulin levels without elevating them through toxic effects on dividing cells.
5. Interferon
Can be used to treat mixed cryoglobulinemia.