AA Amyloidosis

Amyloidosis is the name given to a group of rare disorders in which amyloid deposits, consisting of misfolded proteins which are relatively insoluble, deposit and accumulate in tissues and organs of the body. As these deposits progressively build up they interfere with the working of the organs. Without treatment this will eventually lead to organ failure.

  • AA amyloidosis is one of these disorders. Once known as secondary or reactive systemic amyloidosis, AA amyloidosis occurs in reaction to a long standing chronic infection or inflammatory disorder such as rheumatoid arthritis, Crohn’s disease, bronchiectasis, juvenile idiopathic arthritis, ankylosing spondylitis (AS), inflammatory bowel disease, familial periodic fever syndromes, chronic infections and certain neoplasms. There is no real understanding of why some people with a long standing inflammatory disorder will never develop AA amyloidosis while someone with a similar condition will do so.
  • AA amyloidosis was once one of the most common types of amyloidosis but during the 20th century the incidence of this diseases has dropped since the introduction of more effective treatments for inflammatory and infectious diseases.
  • AA amyloidosis is not a hereditary disease but some of the underlying inflammatory diseases can run in families.
  • AA amyloidosis can occasionally occur in people without a known inflammatory disorder or chronic infection.

What causes AA Amyloidosis?

In people with long term inflammatory diseases, changes take place in the blood chemistry. Healthy levels of a blood protein called serum amyloid A protein (SAA), an acute phase protein, slowly increase from a normal to an excessive level. If the level of SSA remains excessive for many years it may be converted into AA, a protein which will start to deposit progressively as amyloid fibrils in organs and tissues of the body, gradually interfering with function.

People can be diagnosed with AA amyloidosis and not have any known inflammatory or infectious disease. There is some evidence that long term obesity triggers the development of the AA amyloid protein in some people.

What is Amyloidosis?

Organ Involvement

AA amyloidosis is a systemic disease, meaning that any organs and tissues of the body can be affected by the amyloid deposition.

The most common organs involved in AA Amyloidosis are:

  • Kidneys Nephrotic syndrome are the most common organs involved.
  • Spleen.
  • Gastrointestinal tract.
  • Liver

The heart and the peripheral and autonomic nervous systems are rarely involved in AA amyloidosis.

Organ involvement

Symptoms

Symptoms may be non-specific at first and are often complicated by the symptoms from the underlying inflammatory disease.

The most common symptoms and signs are:

  • Protein in the urine.
  • Swollen ankles and legs
  • Weight loss.
  • A feeling of bloating.
  • Nausea.
  • Breathlessness.
  • Kidney failure.

Diagnosis

If a patient presents with protein in the urine and a long standing chronic disease AA amyloidosis may be thought of before any tests are run. However, AA amyloidosis can only be definitively diagnosed through a tissue or organ biopsy, usually the kidney.

Tissue Biopsy

  • A tissue biopsy involves taking a small piece of tissue which, if AA amyloidosis is suspected, may be taken from the kidney.
    • This biopsy is stained with a dye called Congo red in the laboratory.
    • If amyloid is present, the biopsy will appear red under normal light and green (apple-green birefringence) under special polarized light

2nd procedure in the laboratory

  • Further testing is done on the biopsy to identify the type of amyloidosis by identifying the protein composition of the amyloid fibrils.
  • It is imperative to identify the “type” as treatment is different for each type of amyloid.

A number of tests will be run in conjunction with the biopsy to help with the diagnosis, to assess organ damage and plan treatment.

  • Blood tests, particularly kidney tests, albumin and cardiac biomarkers.
  • Urine test to measure protein.
  • Blood proteins to measure Serum Amyloid A (SAA) and CRP (C-reactive protein).
  • ECG and Echocardiogram.
  • History of any previous inflammatory diseases or infections.

Treatment

As in all types of amyloidosis the goals of treatment are:

  • To try and reduce the production of the amyloid forming AA protein or to interfere with the misfolding process and therefore stop the amyloid depositing into the organs and tissues.
  • To support and preserve the affected organs.
  • To maintain and improve quality of life.

Who treats the patient with AA amyloidosis

Once the diagnosis has been made, preferably by a specialized amyloidosis team, ongoing treatment will be given by the appropriate specialists for: a) the underlying disease – often this will be an immunologist or rheumatologist; and b) the affected organs – often this will be a renal physician.

In AA amyloidosis treatment is focused on controlling the underlying disease, which will hopefully lead to a subsequent reduction of the SAA levels resulting in the stabilization or even regression of amyloid deposition.

Treatments to target the underlying disorder may include:

  • Infectious disease – antibiotics.
  • Autoimmune diseases – methotrexate and other disease modifying agents.
  • Neoplasms. Surgery and chemotherapy.

Supportive care is very important to help with the symptoms of the inflammatory disorder and those caused from the organs effected by the deposition of the amyloid protein.

  • Monitoring fluid balance.
  • Diuretics may be needed from time to time.
  • Diet.
  • Testing kidney function regularly with blood and urine tests.
  • Pain relief.
  • Dialysis for failed Kidney function.

Once the underlying inflammatory disease is controlled and the SAA is reduced too near normal there is a chance that amyloid already deposited in the organs will leech out and the kidney function will improve. The outlook for those with AA amyloidosis is then good. However, even if the underlying disease is completely controlled, the kidney damage may not improve and some patients may require dialysis or are considered for a kidney transplant.

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If the underlying inflammatory disease is completely under control and the SAA is no longer being produced but the patient is still in kidney failure and will need dialysis for the rest of their lives a kidney transplant may be considered.