What Is Cryoglobulinemia?
Cryoglobulinemia is a rare disorder characterized by vasculitis (inflammation of the blood vessels), which can harm multiple vital body organs and tissues. In cryoglobulinemia, abnormal immunoglobulins, known as cryoglobulins, coagulate together at very low temperatures, impeding the vascular blood supply and thereby damaging the nervous tissue, muscular tissue, skin, and various organs. It affects the kidneys more commonly. The heart, brain, and gastrointestinal tract are other body organs that can also be affected by the condition less frequently. This disease is commonly denoted as cryoglobulinemia among healthcare practitioners. However, it is better to term it a cryoglobulinemic disease.
There are two reasons for the upper suggested terminology:
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Firstly, cryoglobulinemia is a term used to indicate the low levels of cryoglobulin proteins circulating in the blood of an individual who does not show any symptoms or signs of any disease or condition.
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Secondly, short-lived cryoglobulinemia that is asymptomatic can develop in otherwise healthy individuals after they encounter certain infectious diseases.
What Are Cryoglobulins?
Cryoglobulins are abnormal proteins in the patient’s serum that precipitate at temperatures (below 37°C) and then dissolve again on reheating. They are either composed of a mixture of immunoglobulin and complement system components or immunoglobulins only. These abnormal proteins precipitate in the blood vessels of the affected individual throughout the body, causing endothelial cell injury of the blood vessel wall and thereby resulting in multiple system organ failures. This condition is known as cryoglobulinemia. Patients exhibiting ulcers on the skin, pain in the joints, glomerulonephritis in the kidneys, and peripheral neuropathy should be checked for this deadly disorder.
What Is the Frequency of the Disorder Cryoglobulinemia?
Cryoglobulinemia disorder has a frequency of approximately 1 per 100,000. Females are more commonly affected than males. The disease most commonly occurs in older people above 50-60.
What Are the Causes of Cryoglobulinemia?
Cryoglobulinemia can be either idiopathic with an unknown molecular mechanism or related to other diseases, such as
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Hepatitis C infection (a viral infection causing liver inflammation and damage).
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Lymphomas (cancer of the lymphatic system).
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Multiple myeloma (cancer of a type of white blood cells).
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Systemic lupus erythematosus (autoimmune disease causing widespread inflammatory damage to the organs).
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Sjogren's syndrome (a syndrome characterized by dry mouth and dry eyes).
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Rheumatoid arthritis (an autoimmune inflammatory disease of the joints).
What Is the Classification of Cryoglobulinemia?
The condition can be classified into three main types. They are classified based on the antibody synthesized by each type:
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Type I
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Type II
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Type III
What Is the Pathophysiology of Cryoglobulinemia?
Due to the enhanced production of higher levels of abnormal monoclonal or polyclonal immunoglobulins in chronic infections, cryoglobulins formation occurs. As a result, antigen-antibody complexes are formed. These immune complexes are not cleared out of the patient’s serum sufficiently, thereby leading to the precipitation of cryoglobulins.
What Are the Symptoms of Cryoglobulinemia?
The clinical manifestations of the disease include
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Respiratory problems.
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Cough.
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Tiredness.
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Arthralgia.
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Myalgia.
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Glomerulonephritis (inflammation of the kidney units glomeruli).
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Isolated hematuria (presence of blood in the urine without proteinuria, high blood pressure, or kidney dysfunction).
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Erythematous pruritic purpura.
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Skin rashes and ulcers.
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Raynaud’s phenomenon (reduced vascular supply to the fingers).
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Skin infarction.
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Headache and confusion.
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Xerostomia (dry mouth).
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Xerophthalmia (dry eyes).
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Petechiae (red or brown pinpoint bleeding spots appearing on the skin).
What Is Mixed Cryoglobulinemia?
Mixed cryoglobulinemia includes both Type II and Type III cryoglobulinemia variants. It is a rare disease. Several factors, such as hereditary, chronic infections, environmental stimuli, and autoimmune disorders, occur together, thereby leading to the development of this disease.
The mixed variant presents signs and symptoms that manifest clinically because of the deposition of abnormal cryoglobulins within the walls of the blood vessels.
Meltzer’s triad is clinically presented in mixed variant cases, including palpable purpura, arthralgia, lethargy, fatigue, and weakness. This classical triad is observed in almost 33 % of the affected patients. Cutaneous lesions, including hemorrhagic crusts, rashes, purple purpura, ulcers, and necrotizing gangrene of the digits of extremities, occur in almost 60 to 80 % of the disease cases. Peripheral neuropathy, renal diseases (mainly glomerulonephritis in 30 % of cases), joint pain, and xerophthalmia (dry eyes) are less commonly observed. The glomerulonephritis that occurs in the mixed variant of the disease is caused due to inflammation of the blood vessels. The glomerulonephritis that occurs in the type I variant of the disorder is caused due to obstruction in the vascular supply of blood.
What Are the Diagnostic Tests for Cryoglobulinemia?
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Physical Examination: The healthcare provider should clinically examine the patient thoroughly when diagnosing this disease. Care should be taken if clinical symptoms like purpura, joint pain, erythematous rashes, skin ulcers, and muscle pain are associated with an underlying hematologic disorder.
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Cryoglobulin Test: Measurement of cryoglobulin to show the presence of cryoglobulins should be done essentially. This is known as the cryoglobulin test, which is a laboratory procedure that includes several steps. To perform the cryoglobulin test, the technician usually collects approximately 20 mm (milliliters) of blood and maintains it at 37 degrees Celsius. Anticoagulants are not added to the blood. It is then followed by the centrifugation and refrigeration of the serum to allow coagulation of the abnormal cryoglobulin.
Results:
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Type I Cryoglobulinemia - Will exhibit precipitation of the cryoglobulin proteins within 24 hours. It may also take a window of 3 to 5 days.
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Type II and Type III Cryoglobulinemia - They will present the precipitate within 5 to 7 days after initial refrigeration of the patient’s serum.
The cryoglobulin values in the laboratory are determined as follows:
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In individuals without cryoglobulinemia, the cryocrit value is usually close to zero. However, a value > 0.5 to 1 percent is considered markedly significant.
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In type II Cryoglobulinemiathe cryocrit value usually falls between 2 to 7 percent.
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In type III Cryoglobulinemia, the cryocrit value usually falls within 1 to 3 percent.
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However, there is no established correlation between the calculated laboratory cryocrit levels and clinical manifestations.
Other lab testing procedures include
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An extensive immunochemical analysis is another molecular diagnostic test that can be used to evaluate the disease.
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Analysis of the urine.
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Rheumatoid factor levels.
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Viral serology.
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Determination of the reactants in the acute phase.
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Biopsy of the lesion in special cases where histologic examination of the lesion reveals thrombosis and small-vessel leukocytoclastic vasculitis.
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Electromyography (EMG) can also be done to assess the nervous system damage caused by the disease.
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Angiogram.
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Chest X-ray.
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Hepatitis C tests can also be performed.
What Is the Treatment of Cryoglobulinemia?
The treatment and management of the disease depend on the nature and severity of the existing primary disorder and the extent of end-organ involvement.
1. Elimination of Underlying Pathology: In mixed cryoglobulinemia cases with symptoms, the treatment therapy aims to control the existing autoimmune or infectious diseases.
2. Plasmapheresis: In plasmapheresis, blood plasma is extracted from blood circulation, and abnormal cryoglobulin immunoglobulins are removed and replaced with donated plasma.
3. Immunosuppressive Drugs: Suppression of immunity of the patient with immunosuppressive drugs is also considered one of the treatment modalities by the doctor.
Conclusion:
The survival rate of individuals suffering from cryoglobulinemia is 70 percent after ten years and 50 percent after ten years after the treatment therapy. Delays in the treatment can lead to kidney and hematologic disorders. The disease symptoms and underlying pathology should therefore be treated timely on an urgent basis. There is no well-established treatment for the disease. Extensive research is required on the therapeutic aspects of the disease.
