Information for patients

on amyloidosis and Odense Amyloidosis Center, Odense University Hospital

Amyloidosis is a rare protein accumulation disease. The word amyloidosis derives from the fact that the accumulated protein creates a homogenous mass, called amyloid, which can be detected using microscopy on a tissue sample. A number of different proteins can accumulate as amyloid. In case of a suspected accumulation disease where amyloid has been detected, the next step is to determine the type of protein that forms the building blocks for the accumulation. It may be many different proteins, and therefore many different underlying illnesses that cause the accumulation.

Accumulation of amyloid occurs in different tissue and organs. For some patients, it is a case of just a single organ experincing accumulation, whereas for others, multiple organs may be involved. Some organs are more frequently affected than others. Frequently affected organs are kidneys, heart, liver, skin, tongue and intestines.

Amyloidosis is classified according to the accumulating protein, and according to the underlying illness causing accumulation. There are several, widely different illnesses, which each have their own typical presentation, e.g. in relation to age and most frequently affected organs.

Early and reliable diagnosis is crucial for effective treatment of the disease. Treatment of amyloidosis has generally become more effective and has experienced great progress in recent years.

Amyloidosis is classified according to the type of accumulated protein and according to the underlying disease. These are all relatievly rare illnesses, but some occur more frequently than others, and these are briefly described below.

AL amyloidosis stands for Amyloid Light Chain Amyloidosis. The accumulating proteins are small proteins, known as light chains, and can be one of two types: either kappa or lambda. They are created by a type of white blood cells, called plasma cells in the bone marrow. Everyone has plasma cells, in their bone marrow, that create kappa and lambda protein. Plasma cells are important to our immune system, as they create the natural antibodies that protect us against infections. In patients with AL amyloidosis, dysplasia takes place, which leads to formation of a changed protein with an abnormal composition and form. This means that the proteins have a tendency to accumulate. The underlying problem is the dysplasia of the plasma cells, and this type of amyloidosis can be treated with a type of chemotherapy, which destroys the transformed plasma cells. The dysplasia is not malignant, and AL amyloidosis is not a cancer, but the illness is serious due to the accumulation.

ATTR amyloidosis stands for Amyloid Transthyretin Amyloidosis. Transthyretin is a bigger protein than the light chains. We all create transthyretin, which is the originator of the most dominant protein we have in our serum, i.e. albumin. Transthyretin is also known as prealbumin. There are two types of transthyretin amyloidosis: a hereditary type and an acquired age-related type. The hereditary type is caused by an abnormality in the gene that codes the formation of transthyretin. The transthyretin protein, which is formed, therefore has a slightly different structure than normally, and it is this difference that is significant enough that the protein has a tendency to cause accumulation. There are two main types of the hereditary type; one that most frequently attacks the nerve pathways and leads to chronic nerve stress , and another type, which most frequently affects the heart and causes enlargement of the heart as well as heart failure. Even though this type of amyloidosis is inherent, symptoms occur relatively late in adulthood, e.g. at 40-60 years of age. The non-hereditary type of ATTR amyloidosis is typically seen in older patients and is therefore named “Senile amyloidosis”. It typically also affects the heart.

AA amyloidosis stands for Apoprotein A amyloidosis and is also known as secondary amyloidosis. Occurs in patients with long-term chronic infections, chronic inflammations and chronic, active rheumatism. This type is more frequent in developing countries, but has become rarer in Denmark, as treatment of infections and rheumatism has improved significantly. In connection with AA amyloidosis, it is important to ensure that the underlying triggering illness is treated as well as possible.

Beta 2 microglobulin amyloidosis is caused by accumulation of the protein, Beta 2 microglobulin. This type is typically seen in patients with chronic kidney disease and is caused by the amount of Beta 2 microglobulin in the blood increasing in connection with kidney failure.

Symptoms of amyloidosis vary greatly and depend on which tissue and organs are affected, and to what degree, meaning, how much amyloid is accumulated. The symptoms can be anything from light and rather diffuse to severe and associated with poor function of one or more organs.

Fatigue, reduced work ability, weight loss and dizziness are frequent, common, but uncharacteristic symptoms.

Other symptoms are characteristic in their effect on the organs:

Heart: Shortness of breath, swollen legs (edema)
Kidney: Foaming urine; swollen legs and general water retention.
Skin: Spontaneous hemorrhaging of the skin, frequently around the eyes. Tingly feeling in the hands (Carpal tunnel syndrome). Soft lump formation.
Intestines: Loose stool/diarrhea
Tongue: Tongue growth
Lungs: Shortness of breath

It is crucial to demonstrate amyloid accumulation in a biopsy. It may be a biopsy from a suspected involved organ, e.g. kidney or heart, or from an easily accessible area from skin or rectum. Widespread, general accumulation can usually be demonstrated via a skin biopsy instead of a kidney biopsy, which has a greater risks of causing hemorrhaging. However, a biopsy from the involved organ is often necessary.

Once a biopsy has demonstrated presence of amyloid, the next crucial step is to determine which type of protein the amyloid consists of. This can be done using different advanced techniques using stain microscopy, electron microscopy or mass spectrometry. Electron microscopy or mass spectrometry is considered the most reliable method for precise and certain diagnostic of the protein. In case of a protein that can be associated with a hereditary disease, a genetic investigation into this disease will be initiated.

In case of an amyloid being demonstrated in an organ, a rather comprehensive examination program will be initiated to maintain how widespread the accumulation is in the body, if other organs are affected, and to what degree.

When deciding which treatment to implement, it is crucial to know the exact diagnosis. AL amyloidosis can be treated with chemotherapy, whereas this would have no effect on ATTR amyloidosis.

For all patients, the supporting treatment is essential and must be carefully customized for each patient. There is a number of medications that should be avoided for amyloidosis patients, as they can worsen the condition.

Careful adjustment of the treatment requires expert knowledge and often participation of doctors from multiple specialties during the planning phase. It is often necessary with frequent consultations, for certain periods, to fine-tune the treatment.

Many new medications are being developed and tested for the different types of amyloidosis. Promisingly, new medication is being tested, which is to attempt to actively dissolve the amyloid accumulation, achieving improved organ function.

In the case of AL amyloidosis, the treatment for the triggering plasma cell illness in the bone marrow has improved greatly in recent years, and the prognosis for AL amyloidosis patients is much improved. The earlier commencement of treatment, the better.

The Amyloidosis Center in Odense offers quick, coordinated diagnosis for patients with suspected amyloidosis. Multiple medical specialties are part of a direct multidisciplinary collaboration regarding each patient. All participating doctors are specialists with great interest in and experience with amyloidosis.

The most advanced techniques are used for exact characterization of demonstrated amyloid. Both electron microscopic and mass spectrometric examinations are used for determination of the accumulated protein. The accumulationes are cut into biopsy material, using a laser, cleaned and analysed at the molecular level.

Thorough assessment for involved organs. A thorough assesment is always performed with regards to heart involvement. Several techniques have been establisehd for examination hereof, using scans.

Genetic diagnosis is performed quickly when relevant.

Multidisciplinary treatment, carefully targeted to each patient. Close follow-up of the effect of the treatment and careful adjustment of supporting treatment.

Multidisciplinary day clinic with ample time for review of each patient’s issues and needs.

Good possibilities for participating in new experimental treatments, if good standard treatment has not been established.

AmyC OUH participates in international research collaborations and will therefore always be up-to-date on the newest knowledge about the illness and on treatment options.