AA Amyloidosis

By Dr Sophie Georgin-Lavialle  - Tenon Hospital PARIS - FRANCE

What is AA amyloidosis?

In AA amyloidosis a protein called serumamyloid A serum (SAA) is produced in excessive quantities by the liver. This AAS protein circulates in over-large quantities in the blood. It folds badly and forms amyloid fibrils which are deposited in the different organs.

The most affected organs are the kidneys, the digestive tract (stomach and intestines), the liver and the salivary glands.

SAA protein is a protein of inflammation so that any situation causing chronic inflammation can bring about an excessive production of SAA. The most frequent situations are chronic infections (particularly lung infections), chronic inflammatory rheumatism (rheumatoid arthritis, spondyloarthritis), chronic inflammatory diseases of the intestine (Crohn’s disease, ulcerative colitis), auto-inflammatory diseases of genetic origin, like familial Mediterranean fever and rarer causes such as certain tumours.

The symptoms encountered during AA amyloidosis are often vague and not very specific at first.

When there is advanced kidney failure, patients can suffer from oedema of the ankles, frothy urine and intense fatigue. When the digestive tract is affected diarrhoea may occur.

The most serious complication of AA amyloidosis is terminal kidney failure which may require renal dialysis.

Inflammatory diseases associated with AA amyloidosis

Chronic infections

Bacterial infections Tubercolosis
  Leprosy
  Syphilis
  Osteomyelitis
  Bronchiectasis, cystic fibrosis
  Frequent urinary infections
  Xanthogranulomatous  pyelonephritis
  Endocarditis
  Whipple’s disease
  Chronic skin infections
  Infection of a prosthesis
  Agammaglobulinemia
  Hypogammaglobulinemia
Infections due to parasites or fungus  
Viral infections HIV : humain immunodeficiency virus

 

Chronic inflammatory diseases

Joint diseases (rheumatic) Rheumatoid arthritis
  Chronic juvenile arthritis
  Ankylosing spondylitis
  Psoriatic arthritis
  SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis
  Polyarticular gout
Inflammatory diseases of the digestive tract Crohn’s disease
  Ulcerative colitis
Genetic auto-inflammatory diseases Familial Mediterranean fever
  TRAPS
  Cryopyrin related diseases
  Mevalonate  kinase deficiency
Rare inflammatory diseases Castleman’s disease
 

Still’s disease

  Schnitzler syndrome
  Dermatoses: psoriasis, epidermolysis
  Sarcoidosis
Auto-immune diseases Systemic lupus erythematosus
  Mixed connective tissue disease
  Polymyositis
Vasculitis Takayasu’s disease
  Horton’s disease
  Behçet’s disease
  Other rare vasculitis

 

Tumours

Malignant tumours Kidney cancer
  Horton's disease
  Hodgkin’s disease
  Waldenström’s disease

 

Obesity

Diagnosis of AA amyloidosis

The symptoms of AA amyloidosis may be mistaken for those of more frequent diseases affecting the kidneys, heart, lungs or liver and thus delay the diagnosis of amyloidosis. Indeed, patients often see several doctors before they are diagnosed.

The only way to obtain with certainty a diagnosis of amyloidosis is by carrying out a biopsy.

Once amyloidosis has been found in an organ, it is necessary to find out which kind of amyloidosis it is, using further techniques. In the case of AA amyloidosis, it is necessary in the biopsy to look for deposits of protein SAA, which also needs to be measured in the blood to see if there is too large a quantity in the bloodstream. Another inflammation protein is also measured, reactive protein C.

It is also useful to look at former levels of CRP to see whether they have been high for a long time. Generally, in AA amyloidosis, there has been inflammation for several years before the formation of amyloidosis finally occurs.

Treatment of AA amyloidosis

The purpose of the treatment is to decrease the surplus in the bloodstream of the misfolded protein SAA.

To prevent the amyloidosis from worsening, it is necessary to stop the production of protein SAA by the liver. This means that the inflammation must be stopped and therefore the disease causing the inflammation has to be cured. To do so, specific treatments are available for the different inflammatory diseases: in the case of familial Mediterranean fever for example patients are given lifelong colchicine treatment.

Other treatments vary according to the disease and may include antibiotics (in case of infectious diseases), corticoids or biotherapies. 

So far, no effective treatment has been found to get rid of the amyloid fibrils already formed in the AA amyloidosis.

Finally, a kidney can sometimes be transplanted in case of terminal kidney failure on patients who are otherwise in good health.

Preventive treatment is very important, especially when the patients have had a genetic auto-inflammatory disease since their childhood. Treatment against inflammation is prescribed for the whole of their lives to ensure that they do not develop amyloidosis. Every year, they are required to undergo blood and urine tests to see whether amyloidosis is present.

Monitoring and evolution of AA amyloidosis

In cases of confirmed AA amyloidosis, the patient must be closely monitored by the doctor who is following his or her inflammatory disease, the general practitioner and a specialist in AA amyloidosis.

Questions frequently asked by patients about AA amyloidosis

Why don’t I feel any pain?

Because, as a general rule, deposits of amyloidosis do not cause any pain. They are deposited silently in the soft organs like the kidneys and the digestive tract. This mainly causes tiredness.

Why can’t amyloidosis be seen from the outside?

Because amyloidosis is deposited around blood vessels and in the soft organs. The only visible signs can be the consequences of the infiltration of the skin with bruising or swollen ankles due to malfunctioning of the kidneys. More rarely deposits may also occur around the thyroid gland causing it, and consequently the neck, to increase in size.

How did my inflammatory disease cause AA amyloidosis?

Inflammatory diseases which have not been controlled lead to surplus secretion of protein AAS in the blood. A surplus of this protein has the property of building up into fibrils as time goes by and forming plaques of AA amyloidosis.

Will treatment for my inflammatory disease make my amyloidosis disappear?

The purpose of the treatment for inflammatory diseases is to remove protein SAA from the blood and prevent the appearance of new plaques of amyloidosis. It can stabilise pre-existing amyloidosis and sometimes lessen the malfunctioning of the kidneys when the disease has not reached too advanced a stage.

Will I ever be able to get off dialysis?

To get off dialysis, the kidneys have to be functioning again. As a rule, when they have not been functioning for a long time, they cannot start working again on their own: but a kidney transplant can be beneficial in some situations and dialysis will thus be stopped.

Will I be able to have a kidney transplant?

It is possible to have a kidney transplant for some causes of AA amyloidosis if the patient’s state of health permits. When the cause is a genetic disease, if the subject is young and his or her inflammatory disease is under control, then the patient is more likely to benefit from a kidney transplant.

In AA amyloidosis that is secondary to familial Mediterranean fever (FMF), do I have to stop taking colchicine?

No. Colchicine treatment must be continued as long as the renal function allows it, even in very small doses, as it is the only medicine so far to have proved it can prevent the appearance or worsening of AA amyloidosis in FMF.

Can AA amyloidosis be transmitted to my children?

In the vast majority of cases, AA amyloidosis is secondary to an inflammatory disease, so it cannot be transmitted directly to your children. On the other hand, if you have a genetic inflammatory disease which is complicated by AA amyloidosis, like familial Mediterranean fever (FMF), this can be transmitted to your children. If the latter have FMF, they must take colchicine for their whole life, in order to prevent the appearance of AA amyloidosis and be monitored regularly every year to detect any chronic inflammation and kidney problems.

Do I have to follow a special diet?

No, not unless it is recommended by your nephrologist. But, as with all chronic diseases, be careful not to eat foods containing too much fat, sugar or salt.

Will my treatment be free of charge?

Yes. At your doctor’s request, you will not have to pay for the AA amyloidosis treatment.

Will AA amyloidosis shorten my life expectancy?

AA amyloidosis is a serious disease particularly if you have advanced kidney failure and are on dialysis. You must see your specialist doctor, nephrologist and the internist who is treating your inflammatory disease so that s/he can check for any worsening of your amyloidosis. It is essential to balance the chronic inflammation by curing the underlying inflammatory disease responsible for AA amyloidosis.