What is Amyloidosis

Amyloidosis refers to a group of disease where there is abnormal deposition of an insoluble protein in various body tissues and organs. Excessive deposition of amyloid may lead to serious changes in organ structure and function. There are over 20 types of different proteins involved, each causing a type of amyloid disease. The type of amyloid disease is defined by the major fibrillar protein contained. Amyloidosis can be systemic (where there is protein deposition in various parts of the body) or organ-specific (limited to one organ).

Statistics on Amyloidosis

Amyloidosis is a relatively rare condition, with the number of new cases per year being about 8 in a million. Patients are usually affected after middle age, and the disease appears to affect all races equally. In developed countries, light chain amyloidosis (AL) is the most common type of systemic amyloidosis, while in developing countries another type called AA amyloidosis is more frequent.

Risk Factors for Amyloidosis

The modern way of classifying amyloidosis is based on the biochemical structure, i.e. the main fibril protein involved. The amyloidoses are referred to with 2 capital letters: a capital A (for amyloid) followed by an abbreviation for the fibril protein contained. For example, in a type of amyloidosis called light chain amyloidosis (abbreviated AL), the capital A stands for amyloid, and the capital L stands for the fibril protein which, in this type of amyloidosis, is immunoglobulin light chain or light chain fragment (abbreviated L), hence the abbreviation AL. The most common types of amyloidosis seen are the AL and AA types.
As mentioned above, AL amyloidosis (formerly known as primary amyloidosis) is due to deposition of protein derived from immunoglobulin light chain fragments. It can occur alone or in association with other diseases e.g. multiple myeloma, Waldenstrom’s macroglobulinaemia, or non-Hodgkin’s lymphoma.
In AA amyloidosis (formerly known as secondary amyloidosis), the main fibril protein is serum amyloid A protein (abbreviated A), giving rise to the abbreviation AA for the disease. Amyloidosis may occur as a result of chronic diseases with ongoing inflammation, such as rheumatoid arthritis (RA), osteomyelitis, tuberculosis, Hodgkin’s lymphoma, kidney cancer, leprosy, Crohn’s disease, AIDS, lupus etc.
There are other types of amyloidosis, e.g. dialysis-related amyloidosis (which occurs in patients on long-term dialysis), familial amyloidosis (caused by inherited gene abnormalities), systemic senile amyloidosis (which is an age-related amyloidosis).

Progression of Amyloidosis

In the two most common forms of systemic amyloidosis, AL and AA amyloidoses, the major sites involved are the kidneys, heart, and liver. Amyloid deposition can be limited to a single organ, such as the skin, eye, heart, pancreas, reproductive tract and urinary tract. Hereditary amyloidosis is characterised by impairment of nerves, as well as amyloid deposition in the heart, vessels, and kidneys. Carpal tunnel syndrome may occur.

How is Amyloidosis Diagnosed?

If signs and symptoms point to amyloidosis, the diagnosis has to be confirmed by a biopsy, which is taking a sample of tissue. Noninvasive tests such as echocardiography of the heart and X-ray of bone abnormalities may provide supportive information but are not sufficient for the diagnosis of amyloidosis.
The samples of tissues (biopsies) may be taken from the non-functioning/abnormal organs (eg. kidney, nerve) or from uninvolved sites such as fat pad below the skin of the tummy (subcutaneous abdominal fat pad), or the superficial layer of the backpassage (rectal mucosa). Tissue sections are then stained with a special dye and viewed under polarised light. If amyloid is present, it will glow green.

Prognosis of Amyloidosis

Prognosis is largely dependent on the extent of organ damage when amyloidosis is first diagnosed. If amyloidosis is secondary to another disease, successful treatment of the underlying disease is important to improving outcome. The most common causes of death are kidney and heart failure.

How is Amyloidosis Treated?

Treatment varies depending on the type of fibril protein.
For primary amyloidosis (AA), the options are stem cell transplantation and chemotherapy (with e.g. dexamethasone, melphalan, prednisone). Complete clinical recovery has been shown in some patients following stem cell transplantation, with improvement in quality of life.
The most important therapeutic modality for AL (secondary amyloidosis) is treatment of the underlying inflammatory process (e.g. rheumatoid arthritis or chronic infection). This improves the kidney function and helps get rid of the amyloid deposits from the body. A type of medication called colchicine has also been used, particularly in familial Mediterranean fever. Newer agents that stop the production of fibril protein are still under development. In some cases, dialysis and renal transplantation may be considered.
Management of dialysis-related amyloidosis involves altering the mode of dialysis or considering renal transplantation.
For the hereditary amyloidoses in which the abnormal protein is produced by the liver, liver transplantation may control the disease by preventing further deposition of amyloid.

Amyloidosis References

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