Cryoglobulinemia is a medical condition in which blood contains large amounts of cryoglobulins-proteins that become insoluble at reduced temperatures.

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Cryoglobulinemia can be associated with various diseases such as multiple myeloma and hepatitis C infection.

Occurred In

The female to male ration of occurrence is 3:1
The most common age group to be affected by cryoglobulinemia is between 42-52 years of age.

Classification of cryoglobulinemia

Cryoglobulinemia is classifically grouped into three types according to brouet classification and the three types are as follows
• Type І cryoglobulinemia is most commonly encountered in patients with a plasma cell dyscrasia such as
Multiple myelomas
Waldenstrom macroglobulinemia
• Type ΙΙ and type ІΙІ of cryoglobulinemia are strongly associated with infection by the hepatitis C virus.
• Type ΙІΙ of cryoglobulinemia is associated with autoimmune diseases such as given below
Systemic lupus erythematosus
Rheumatoid arthritis

Causes of cryoglobulinemia

Disease associations’ variable based on type of cryoglobulinemia are given as under
• Type І cryoglobulinemia is seen in lymphoproliferative disorders example multiple myeloma, Waldenstrom macroglobulinemia.
• Type ΙІ and ΙІΙ are observed in chronic inflammatory diseases such as chronic liver disease
Coexistent connective- tissue diseases
Mixed cryoglobulinemia is rarely associated with lymphoproliferative disorders.
Infections in which cryoglobulinemia is seen
• Viral infections are as follows
Hepatitis A, B, C
• Bacterial infections
Lyme disease
Streptococcal infections

• Fungal

• Parasitic
Autoimmune diseases
• SLE, rheumatoid arthritis, Sjogren’s syndrome
• Vasculitis- polyarteritis nodosa, Henoch-schonlein purpura

Cryoglobulinemia sign and symptoms

Skin manifestation
• Livedoid vasculitis
• Cold-induced urticaria
• Hyperkeratotic spicules in areas exposed to cold
• Scarring of tip of nose, pinnae, fingertips, and toes
• Acrocyanosis
• Nailfold capillary abnormalities
• Palpable purpura
• Ischemic necrosis

Pulmonary manifestation
• Dyspnea
• A cough
• Pleurisy
• Pleural effusion
• Bronchiectasis

Gastrointestinal manifestations
• Abdominal pain
• Hemorrhage
• Hepatomegaly or signs of cirrhosis’
• Splenomegaly

Renal manifestations
• Membranoproliferative glomerulonephritis
• Intraluminal cryoglobulin deposition
• Hypertension
• Nephrotic-range proteinuria with resultant edema

Joint manifestation
• Arthralgias
• Frank arthritis and progressive joint deformity

Nervous system manifestations
• Sensorimotor neuropathy
• Visual disturbances
• CNS involvement

Test To Be Done

• Evaluation of serum cryoglobulins
• Urinanalysis
• Complete blood cell count
• Serum chemistry
• Liver function studies
• Rheumatoid factor
• Antinuclear antibody
• Erythrocyte sedimentation rate
• Complete evaluation

Other studies to be done are as follows
• Consider serum protein electrophoresis
• Urine protein electrophoresis
• Quantitative immunoglobulin
Serum viscosity

Imaging studies to be done are as follows
• A chest radiograph
• CT imaging
• Transesophageal echocardiography
• Angiography

Tissue biopsy required for diagnosis when patients are evaluated with vasculitis.
Electromyography and nerve conduction studies are also done
Further diagnostic procedures to be done are as follows
• Bone marrow biopsy
• Liver or kidney biopsy.

How To Treat Cryoglobulinemia

Cryoglobulinemia is treated with plasmapheresis.
Severe cryoglobulinemia which involves vital organs or large areas of skin is treated with corticosteroids and other medicines that calm the immune system.

Risk Factors Of Cryoglobulinemia

• Blindness
• Stroke, seizure or coma
• Pericarditis
• Congestive heart failure
• Respiratory distress
• Gastrointestinal hemorrhage
• Acute renal failure
• Severe cutaneous necrosis or gangrene

Differential diagnosis of cryoglobulinemia
• Cirrhosis
• Chronic lymphocytic leukemia
• Churg-Strauss syndrome
• Giant cell arteritis
• Glomerulonephritis, acute
• Diffuse proliferative glomerulonephritis
• Goodpasture syndrome
• Hemolytic-uremic syndrome
• Viral hepatitis
• Non-Hodgkin lymphoma
• Serum sickness
• Sarcoidosis
• Systemic lupus erythematosus
• Antiphospholipid syndrome
• Hepatitis A
• Hepatitis B
• Hepatitis C

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