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CRYOGLOBULINEMIA
Cryoglobulins are antibody complexes that precipitate as serum is
cooled and that dissolve on rewarming (1). These complexes contain
hepatitis C virus (HCV) particles and can precipitate in the walls of
small and medium sized vessels. There are three types (I, II, III) of
cryoglobulinemia .Type II or “mixed” cryoglobulinemia (MC) is the one
most commonly associated with chronic hepatitis C infection. This type
is called “mixed” because the antibodies that are found are of two
kinds. One antibody is a polyclonal (i.e., from more than one group of
cells) antibody (IgG), and the other antibody is a monoclonal (IgM)
directed against the IgG. The frequency with which cryoglobulins are
detectable in serum of patients with CHC depends on how carefully
samples are handled and upon the methods used for detection of
cryoglobulins. Because these proteins precipitate from serum as it is
cooled, the blood must be kept at body temperature after it has been
obtained until it has clotted and the serum has been drawn off. Then
the serum is tested for the abnormal proteins. If this precaution is
not observed, the test may be spuriously negative.
The skin, kidney, nerves and joints can be affected by cryoglobulins.
Cutaneous leukocytoclastic vasculitis is a skin lesion that appears as
palpable purpura (hemorrhages in the skin that result in the appearance
of purplish spots or patches) that usually affects the lower
extremities over the shins (Fig 1). These lesions are caused by
plugging of the dermal capillaries (very small blood vessels in the
skin). Successful treatment of the hepatitis C infection with
interferon (+ ribavirin) usually results in resolution of the skin
lesions.
Cryoglobulins
also affect the nervous system in some HCV infected patients. The most
frequent symptoms and signs are those of chronic sensory
polyneuropathy, although acute or subacute encephalopathy has been
reported as well (2,3). “Restless leg syndrome” and Guillain-Barré
syndrome have also been reported (4). The mechanism of nerve
involvement is thought to be MC-well-established related vasculitis of
the small blood vessels that supply the nerves. There is no
well-established treatment. Treatment with interferon, corticosteroids,
or cyclophosphamide (cytoxan) has not shown any consistent results
although some patients appear to respond to one or a combination of
these drugs (5).
http://www.hcvadvocate.org/hcsp/articles/Bonkovsky-2.html
Cryoglobulinemic Vasculitis
The name literally means “cold antibody in the blood”, which refers
to the chemical properties of the antibodies that cause this disease:
cryoglobulins are antibodies that precipitate under cold conditions.
Drug use is a prime risk factor for cryoglobulinemia because more than
90% of cases of cryoglobulinemic vasculitis are associated with
hepatitis C infections. Hepatitis C is acquired by injection drug use
(needle–sharing), tainted blood products, and (probably rarely), sexual
transmission. Treatment of the underlying hepatitis may be an effective
therapy for this type of vasculitis.
Pictured below is the hand from the same patient at different times. The image on the
left is normal and the one on the right shows the patient in the midst
of a flare of cryoglobuinemic vasculitis.
Pictured below is an electron micrograph of a kidney biopsy specimen from a patient with cryoglobulinemia.
In medical terms, by David Hellmann, M.D.
A
discussion of Cryoglobulinemia written in medical terms by David
Hellmann, M.D. (F.A.C.P.), Co-Director of the Johns Hopkins Vasculitis
Center, for the Rheumatology Section of the Medical Knowledge
Self-Assessment Program published and copyrighted by the American
College of Physicians (Edition 11, 1998). The American College of
Physicians has given us permission to make this information available
to patients contacting our Website.
Cryoglobulins are
immunoglobulins that precipitate in the cold and disolve on rewarming.
Three types of cryoglobulins are distinguished based on whether the
cryoglboulin is monoclonal and has rheumatoid factor activity. Knowing
the type usually allows the physician to predict the clinical features;
alternatively knowing the clinical features allows one to deduce the
type of cryoglobulin. Type I is a monoclonal antibody that does not
have rheumatoid factor activity. Most commonly, type I is associated
with lymphoma, Waldenström's macroglobulinemia, and multiple myeloma.
Because type I cryoglobulins do not easily activate complement,
patients with type I are asymptomatic until the level of
cryoglobulinemia is sufficiently high to cause hyperviscosity syndrome.
Both types II and III are rheumatoid factors — antibodies that bind to
the Fc fragment of IgG. Therefore, both types are called mixed
cryoglobulins. In type II, the rheumatoid factor is monoclonal, whereas
in type III it is polyclonal. Type II is associated with
lymphoproliferative diseases, and both types can occur in patients with
rheumatic diseases and chronic infections. Cryoglobulinemia is said to
be essential when there is no identifiable underlying disease. Type II
and III cryoglobulinemia frequently presents as vasculitis, most
commonly with recurrentlower extremity purpura, glomerulonephritis, and
peripheral neuropathy.
It is now evident that most
patients diagnosed with type II or type III mixed essential
cryoglobulinemia have the disease as an immune response to chronic
hepatitis C infection. The role of hepatitis C virus is suggested by
finding that the cryoglobulins in these patients are enriched with
anti–hepatitis C antibody and hepatitis C RNA. Moreover, antviral
therapy can remit the disease in some patients.
Treatment
depends on the type of cryoglobulin, underlying disease, and severity
of symptoms. Cryoglobulinemia with severe hyperviscosity syndrome
requires plasmapheresis and chemotherapy of the underlying malignancy.
Some patients with cryoglobulinemia suffer from mild, recurrent crops
of lower extremity purpura that require no specific therapy. More
extensive vasculitis associated with autoimmune diseases or essential
cryoglobulinemia may respond to prednisone, cyclophosphamide, or both.
The most effective treatment for cryoglobulinemia associated with
hepatitis C has not yet been determined. Brief use of prednisone
followed by 6 months of interferon alfa has produced clinical and liver
function test improvement, but relapse of liver disease and vasculitis
often occurs when interferon alfa is stopped.
All
information contained within the Johns Hopkins Vasculitis Center
website is intended for educational purposes only. Visitors are
encouraged to consult other sources and confirm the information
contained within this site. Consumers should never disregard medical
advice or delay in seeking it because of something they may have read
on this website.
Thanks to the Vasculitis Centre Website for this information:
http://vasculitis.med.jhu.edu/typesof/cryoglobulinemia.html
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