Amyloidosis is a rare and potentially life threatening disease that occurs when toxic proteins build up in the body's tissues and organs. There are more than 30 different types of these toxic proteins and they affect many different tissues and organs.
These proteins misfold into amyloid fibrils and accumulate within various organs and tissues of the body, which alters their normal functions.
Diagnosing amyloidosis can be challenging because there are a variety of types which can affect different organs. The most common organs affected are the heart, kidneys, liver, nervous system and gastrointestinal tract.
Causes of Amyloidosis
Systemic amyloidosis arises from normal or abnormal proteins that transform into amyloid. Although there are over 30 known proteins that cause amyloid in humans, there are three major types that account for about 90% of cases:
- Immunoglobulin light chain amyloidosis (AL), formerly known as “primary amyloidosis” is the most common form. In AL, excess bone marrow plasma cells secrete the protein that forms amyloid. These bone marrow plasma cells are similar to those in multiple myeloma, a cancer of plasma cells. The most common organs affected in AL are the heart, kidneys and nervous system.
- Transthyretin amyloidosis (ATTR) arises either from a mutation in the transthyretin gene (ATTR-mutated) or from normal transthyretin (ATTR-wild type). The mutated form may be passed down in families and is more common in certain ethnic groups, including African-Americans, Portuguese and Swedes, among others. This form most commonly affects the heart and nerves.
- Secondary amyloidosis (AA) occurs as a result of chronic infectious or inflammatory diseases, such as tuberculosis, rheumatoid arthritis or periodic fever syndromes, or sometimes for unknown reasons, all of which result in production of the serum amyloid A protein. The most common organ affected is the kidney.
- Localized amyloidosis may also occur. It is usually of the AL type and may be found incidentally or be associated with symptoms. Common sites of localized amyloidosis include the upper airways, gastrointestinal tract and urothelial tract.
Diagnosing amyloidosis is a complicated process, as symptoms are frequently vague and appear similar to those of other common diseases spanning the areas of cardiology, nephrology, neurology and more.
Often, it is the presence of many persistent, unrelated symptoms that alert a physician to the possibility of amyloidosis. Amyloidosis is potentially life threatening so receiving a prompt and accurate diagnosis is critical. Advanced diagnostic procedures are sometimes needed to arrive at an accurate diagnosis.
General symptoms may include:
- Foamy urine
- Joint pain
- Low red blood cell count (anemia)
- Shortness of breath
- Swelling in the ankles, legs, and tongue
- Tingling and numbness in hands and feet
- Weight loss
Treatment and Clinical Trials
Once an accurate diagnosis is obtained, a multidisciplinary treatment plan that is personalized is essential. Treatment approaches in amyloidosis depend on the type of amyloidosis, type and extent of organs involved and each patient’s general medical condition. In general, the goal of treatment in amyloidosis is either: (1) eliminate the protein precursor that forms amyloid, which will allow for improvement or stabilization of organ function or (2) interrupt formation of new amyloid to stabilize organ function from further deterioration.
For AL amyloidosis, chemotherapy treatments to eliminate production of the immunoglobulin light chain that forms amyloid remains the standard treatment. There are a wide variety of chemotherapy options including high-dose chemotherapy and autologous stem cell transplant.
For ATTR amyloidosis, there are medications to interrupt amyloid formation and stabilize organ function. In addition, careful management of symptoms of heart failure and neuropathy are important.
In AA amyloidosis, treatment of the underlying disease causing the inflammation is the standard treatment.
In localized amyloidosis, measures to control the local amyloid deposits with surgery or radiation are sometimes needed. Often, patients with localized amyloidosis can be observed without treatment.
There are new treatments in development for amyloidosis that include novel treatments to stop production of the protein precursor to amyloid and stimulate clearance of deposited amyloid. The Penn Amyloidosis Program is participating in many of these new approaches that are currently being tested in clinical trials.
Penn Medicine's multidisciplinary approach allows our specialists to develop an individualized treatment plan for each of our patients.
The Amyloidosis Program at Penn Medicine is located in Philadelphia, PA at the Ruth and Raymond Perelman Center for Advanced Medicine and the Philadelphia Heart Institute at Penn Presbyterian Medical Center.