This disorder was previously known as secondary amyloidosis. It occurs in patients who have suffered from prolonged, chronic inflammatory or infectious diseases for many years.
Introduction to AA Amyloidosis
Most patients with AA amyloidosis have amyloid deposits in their kidneys which cause problems with kidney function, most commonly protein in the urine. There are always amyloid deposits in the spleen, which may be enlarged. There may also be amyloid deposits in other parts of the body, which usually do not cause symptoms.
The amyloid fibrils making up the amyloid deposits are formed from a protein called amyloid A protein which is derived from a normal blood protein of unknown function, called serum amyloid A protein (SAA). SAA is known as the “precursor” protein in AA amyloidosis. SAA is produced in the liver and is found in very small quantities (less than 5 mg per litre) in the blood of all healthy people. But when there is almost any kind of inflammation, infection or injury in the body, SAA production increases greatly, along with the production of another normal trace protein called C-reactive protein (CRP). Production of some other blood proteins also increases, although to a much smaller extent, as part of this normal reaction to disease, called the acute phase response. The level of SAA increases more dramatically than that of any other protein and may reach 2,000 mg per litre.
If there is recovery from whatever disease or injury caused the acute phase response, then levels of SAA drop rapidly. However, if the disease persists, SAA levels remain high. In up to 10% of patients with sustained high levels of SAA persisting for several years, the SAA forms amyloid A fibrils in the tissues and these amyloid deposits cause AA amyloidosis.
Before 1994, AA amyloidosis was the diagnosis in almost 1 in 3 of the patients seen at the NAC. Since then it has progressively become far less common in the UK and other developed countries. This is believed to be a result of the greatly improved therapies available for many of the associated inflammatory diseases, such as rheumatoid arthritis and Crohn’s disease. These therapies can be very effective in lowering SAA production, thereby preventing development of amyloidosis.
Conditions that may lead to AA amyloidosis
Diseases in which chronic inflammation may eventually lead to AA amyloidosis include:
- arthritis, most commonly (in up to 10% of patients with prolonged disease):
- rheumatoid arthritis
- juvenile (childhood) inflammatory arthritis
Hands of a patient with Rheumatoid Arthritis
less commonly the following types of arthritis may lead to AA amyloidosis :
- ankylosing spondylitis
- psoriasis and psoriatic arthropathy
- Reiter’s syndrome
- adult Still’s disease
- Behçet’s syndrome
2. Crohn’s disease
3. hereditary periodic fever syndromes such as Familial Mediterranean Fever (FMF)
4. chronic infections which may be local (limited to one organ), or systemic (throughout the body), most commonly:
- bronchiectasis
- chronic pyelonephritis (kidney infection) in paraplegic patients
- chronic infections in intravenous drug users
less commonly the following chronic infections may lead to AA amyloidosis:
- tuberculosis
- leprosy
- chronically infected burns
- chronic leg ulcers
- chronic osteomyelitis (infection inside the bone)
- Whipple’s disease
5. some types of cancer, most commonly:
- Hodgkin’s disease
- kidney cancer
less commonly the following types of cancer may lead to AA amyloidosis:
- cancer of the gut, lung, urogenital tract
- basal cell carcinoma (BCC)
- hairy cell leukaemia
In some other, related chronic inflammatory diseases, AA amyloidosis is extremely rare. This is probably because the acute phase response of SAA is blunted in these conditions, despite the persistent inflammation. These conditions include:
- ulcerative colitis
- systemic lupus erythematosus
- some other connective tissues disorders
A small number of patients with AA amyloidosis do not have detectable evidence of a prolonged inflammatory disease. Some of these are carriers of inherited fever syndrome genes.
Is AA amyloidosis inherited?
AA amyloidosis itself is never inherited. However, the inflammatory diseases that are associated with AA amyloidosis do tend to run in families. The hereditary fever syndromes in particular have a very clear genetic basis.
Is it possible to predict AA amyloidosis?
Some patients may be exposed to chronic inflammation and high SAA levels for decades yet may never develop AA amyloidosis. Others develop AA amyloidosis after just a few years of chronic inflammation. For example, children with Familial Mediterranean Fever may develop rapidly progressive kidney failure due to AA amyloidosis, even before the FMF is diagnosed and colchicine treatment is established.
The reason for this is unclear. There is some evidence that genetic factors related to variations within the gene for SAA may play a part in determining the likelihood that high levels of SAA will form amyloid deposits. It is not possible at present to predict which patients with chronic inflammation will develop AA amyloidosis if the inflammation is not treated successfully and which will not.
However, it is clear that successful treatment of inflammatory conditions, with suppression of SAA levels does prevent the development of AA amyloidosis. It is therefore very important that patients are always careful about taking all their pills.