Cryoglobulinemia: Causes, Types, Associated Diseases, Effect on Organs, Symptoms, Treatment

Cryoglobulinemia is a disease caused by increased Cryoglobulins in serum. Excessive amounts of abnormal proteins-cryoglobulins in blood become thick and viscous at lower body temperature. The viscous and thick blood increases blood viscosity and causes blocking blood vessels resulting in many serious complications. In this article, we will discuss about the causes, symptoms, and treatments for Cryoglobulinemia.

• It is a pathological condition in which there are excessive amounts of cryoglobulins in the blood, which have a tendency to become thick at low temperatures.
• Cryoglobulinemia is also known to be associated with other diseases like multiple myeloma and hepatitis C.
• It causes systemic vasculitis, which may cause systemic disease.¹

• Hyper-Viscosity- Cryoglobulins circulates in blood and become thick and precipitate at low body temperature. The cause of change in physical characteristics at low temperature is not known.
• Antibodies- Cryoglobulins are proteins that function as antibodies. It increases in autoimmune disease.
• Infection- Cryoglobulin is found in higher concentration in hepatitis C infection.
• Blood Cancers- Cryoglobulin is abnormally increased in patient suffering with lymphoma and multiple myeloma
• Connective Tissue Disease– Concentration of Cryoglobulin is at higher level in patients suffering with connective tissue disorder like lupus.

Cryoglobulinemia is basically classified into three types, Type I, Type II, and Type III.

• Type I Cryoglobulinemia: This is caused by monoclonal immunoglobulin. This type is usually related to cancerous conditions of the blood or the immune systems.
• Types II Cryoglobulinemia: This is caused by IgM, IgG and IgA monoclonal immunoglobulin. These types of Cryoglobulinemia are most commonly found in people who have chronic inflammatory conditions like hepatitis C.
• Types III Cryoglobulinemia: This disease is caused by IgM and IgG polyclonal immunoglobulin.

Following diseases often have increased level of Cryoglobulins in blood²–

• Leukemia
• Multiple Myeloma
• Primary Macroglobulinemia
• Rheumatoid Arthritis
• Systemic Lupus Erythematosus
• Mycoplasma Pneumonia
• Post Streptococcal Glomerulonephritis

• Ischemic Changes- Serum Cryoglobulin causes thick precipitation of serum at low temperatures. Increased blood viscosity eventually start slowing the blood flow or blocks the smaller vessels. The reduced blood supply to tissue and organs causes ischemia (lack of blood supply) and numerous complications including renal failure.
• Tissue and Organ Damage- Cryoglobulinemia is a disease, which damages the tissue secondary to ischemia. Blocking of blood supply to normal tissue and organ causes ischemia.

Patient may be asymptomatic with abnormal blood test suggesting presence of abnormal Cryoglobulin in serum. Symptoms of Cryoglobulinemia, non-specific and systemic, depends on target organ involved in disease.

• Fatigue
• Weight loss

• Skin- Purple bruises, rash and skin ulcer
• Skeletal System- Joint pain, muscle ache, ankle swelling (edema feet) and Raynaud’s phenomenon
• Nervous System- Peripheral neuropathy³, numbness and weakness
• Respiratory System- Dyspnea or short of breath
• Kidney- Glomerulonephritis causes hematuria, proteinuria and kidney failure
• Cardiovascular System- Hypertension
• Gastrointestinal System- Enlarged liver and spleen

• Hepatomegaly- Liver enlargement
• Hypertension- Increased blood pressure
• Splenomegaly- Enlarged spleen
• Numbness- Peripheral neuropathy and numbness

• CBC- Results are often normal
• ESR- Erythrocyte sedimentation rate is increased in Cryoglobulinemia.
• Complement panel, in case of Cryoglobulinemia the values will be low normal.
• Cryoglobulin test to look for presence of Cryoglobulins
• LFTs will be usually high in Cryoglobulinemia.
• Rheumatoid Factor test is positive.
• Skin Biopsy- Test is performed if skin ulcer is non-healing.

• Urinalysis- Hematuria and proteinuria is observed if patient is suffering with Cryoglobulinemia induced glomerulonephritis.

• Test is performed to evaluate tissue perfusion.

• X-ray chest is performed to evaluate short of breath and frequent dry cough.

• Test is performed to diagnose the cause of pain.

• Avoid low temperature
• Patient should move residence to warmer place.

• Corticosteroids⁴
• Treatment for Glomerulonephritis-
• Corticosteroids
• Immunosuppressive medications
• Fluid management
• Electrolyte treatment
• Kidney dialysis
• Antibiotics- Rituximab is effective in treating vasculitis caused by cryoglobuminemia.¹
• Plasma Exchange
• Interferon Alpha

• Rare cases of bleeding in digestive tract
• Rare cases of heart disease
• Infection of ulcers
• Renal failure
• Liver failure

References:

Also Read:

• Cryoglobulinemia: Epidemiology, Causes, Treatment, Investigations