Principles of treatment

Treatment of all types of amyloidosis is currently based on the following principles:

1. Reducing the supply of amyloid forming precursor proteins.
2. Supporting the function of organs containing amyloid.

SAP scans in thousands of patients with various forms of amyloidosis have shown that when amyloid precursor protein supply is controlled:

• existing amyloid deposits often regress (become smaller)
• new amyloid deposits stop appearing
• organ function is often preserved and may also recover

A sink analogy

It may be helpful to envisage amyloid deposits blocking up the organs as somewhat similar to the everyday situation of a blocked sink.

Water running from the tap at full blast represents the uncontrolled production and high level presence of precursor proteins capable of forming amyloid fibrils.  The small sink outlet represents the body’s limited capacity to clear amyloid deposits away from the organs.

If the tap is turned on fully so that the rate of running water far exceeds the drainage rate, water builds up in the basin despite some drainage. If the tap is turned down sufficiently, the water can drain away slowly.

In AA amyloidosis, if the rate of production of amyloid forming proteins due to underlying inflammatory disease can be reduced sufficiently, amyloid stops accumulating in the tissues. Amyloid deposits may even be cleared away faster than they are produced.

Goals of treatment

In AA amyloidosis, the goal of treatment is to control the associated inflammatory disease, leading to a damping down of the acute phase response and a subsequent drop in SAA levels.

When SAA levels are reduced, formation of new amyloid deposits is slowed down and often halted completely. There is frequently regression of existing deposits if the SAA level is maintained close to normal (less than 10 mg per litre). There is then a good chance of improvement in organ function, overall health and length of survival.

The precise treatment given depends on which chronic inflammatory disease is present.

In recent years the outlook for patients with AA amyloidosis has improved dramatically with the introduction of several new and effective drugs that control inflammation and lower SAA levels in the common chronic inflammatory diseases associated with AA amyloidosis such as rheumatoid arthritis and Crohn’s disease.

These drugs include new injectable, biological drugs for arthritis and Crohn’s disease, including:

• anti-TNF drugs such as
  • infliximab
  • etanercept
  • adalimumab
• anti-IL-1 drugs such as
  • anakinra
  • canakinumab

There are specific treatments for some inflammatory diseases which suppress the acute phase response and SAA levels very effectively. This makes development of AA amyloidosis very unlikely as long as patients are careful about taking their medicines as prescribed.

These treatments include:

• lifelong colchicine for Familial Mediterranean Fever (FMF)
• anakinra for some other periodic fever syndromes, such as TRAPS, MKD, DIRA
• canakinumab for CAPS
• appropriate antibiotic drugs for tuberculosis
• surgery for Castleman’s disease and osteomyelitis

 Monitoring during treatment

Doctors at the NAC usually recommend monthly measurement of SAA levels in the blood in order to determine whether the treatment is controlling inflammation adequately.

Patients may sometimes be symptom free, despite on-going inflammation. So SAA levels rather than subjective symptoms should be used to guide treatment decisions. Patients visiting the NAC may be provided with a special kit for sending monthly blood samples in the post. NAC doctors can then recommend appropriate adjustment in treatment dosages, or changes in drug regimes based on the SAA levels. SAA results may be sent directly to patients to encourage their understanding of their progress and involvement in their own management.

Continued monitoring of SAA levels is important even after therapy has led to adequate control of SAA levels. There may be sudden resurgences of inflammation even after a relatively long period of stable disease and improved kidney function.

SAP scintigraphy scan is usually recommended about once a year to quantify the amyloid deposits in the organs. Serial scans can show how effectively amyloid deposits are being cleared and give an indication of the level of inflammation that is acceptable in any particular patient.

Sometimes it is necessary to try various different treatments before SAA levels are effectively controlled. Occasionally low dose chemotherapy drugs may be used to suppress inflammation when other drugs fail.

Treatment of kidney disease in AA amyloidosis

Kidney disease is often the most serious health problem for patients with AA amyloidosis. In some patients, kidney function improves once SAA levels are lowered, even if there is just stabilization of amyloid deposits.

All patients with AA amyloidosis affecting their kidney function should be seen regularly by a nephrologist who is expert in amyloidosis. Important principles include:

• carefully monitoring and maintenance of fluid balance
• regular testing of kidney functions with blood and urine tests
• use of diuretics when required

Abnormal kidney function due to AA amyloidosis may affect the ability of the kidneys to produce urine. This means that the body is unable to cope well with excess fluids. Patients with fluid overload may develop swelling in the legs (oedema) or difficulty breathing due to heart failure.

Fluid excess can be avoided by careful attention to the 3 Ds:

1. Diet

2. Diuretics

3. Daily weights

1. Diet:

Fluid intake should be steady and should usually not exceed 1.5 litres per day.

Salt intake should be limited. This includes attention not just to salt added to the food from the salt shaker, but also to food with high salt content such as crisps, bacon, canned meats, sausages, canned soups and smoked fish. It can be very helpful to meet with a dietician for precise and personalised dietary advice.

2. Diuretics:

Doctors will often prescribe diuretics (water tablets) which help the body to lose excess salt and water. Taking these drugs is not a substitute for avoidance of excessive dietary salt and water.
Removal of excess body fluid reduces ankle swelling and breathlessness.
Furosemide is usually prescribed first, then other diuretics such as spironolactone may be added.
Since diuretics increase the amount of urine produced, they should usually be taken in the morning sometimes with another dose at lunchtime.

3. Daily weights:

Some patients benefit from recording their weight regularly, usually daily or weekly. It is important that weight should be measured consistently- using the same scales, at the same time of day. This is usually best done first thing in the morning after passing urine, just wearing underclothes. Several litres of fluid can accumulate in the body without it being very noticeable. An increase in weight can be an early sign of fluid excess. The doctors or nurse can then recommend appropriate measures such as increased diuretic dose, before the patient even feels unwell because of the fluid overload.

In patients who already developed kidney failure before their AA amyloidosis was controlled, dialysis may become necessary. Kidney transplantation may be successful and it is rare for AA amyloid to significantly affect a transplanted kidney.

Outlook for patients with AA amyloidosis

If not effectively treated, AA amyloidosis leads inevitably to kidney failure, necessitating dialysis or kidney transplantation.

But over the past 10 years the outlook for patients with AA amyloidosis has brightened considerably. Most patients can be treated with drugs that suppress inflammation and lower SAA levels. This slows down, halts or reverses the deposition of AA amyloid. Many patients have survived for decades after AA amyloidosis was diagnosed.

AA amyloidosis has also become far less common in developed countries such as the UK over the last 10 years. This is believed to be a consequence of the widespread use of the new powerful drugs that combat inflammation for diseases such as rheumatoid arthritis. When the inflammation is controlled by these drugs, patients are not exposed to prolonged high SAA levels. So amyloidosis develops far less frequently than it did in the past. In contrast, in developing countries where these drugs are not widely available, AA amyloidosis remains more common.