Amyloidosis is a progressive inflammatory non-age-related sensorineural disorder in which abnormal proteins build up in tissues and organs. The cause of primary amyloidosis is unknown. The condition is related to abnormal and excess production of abnormal antibodies cells by a type of immune cell called plasma cells. Clumps of abnormal proteins build up in certain organs or at the same time multiple organ tissues. This cell reduces their ability to work correctly in another cell. Symptoms depend on the organs affected. This disease most often can affect the tongue, intestines, skeletal and smooth muscles, nerves, skin, ligaments, heart, liver, spleen, and kidneys.
Causes
There are many different types of amyloidosis. Some varieties are hereditary. Others are caused by outside factors, such as inflammatory diseases or long-term dialysis. Many types affect multiple organs, while others affect only one part of the body.
Subtypes of amyloidosis include:
- AL amyloidosis (immunoglobulin light chain amyloidosis). The most common type of amyloidosis in developed countries, AL amyloidosis is also called primary amyloidosis. It usually affects the heart, kidneys, liver and nerves.
- AA amyloidosis. Also known as secondary amyloidosis, this variety is usually triggered by an inflammatory disease, such as rheumatoid arthritis. Improved treatments for severe inflammatory conditions have resulted in a sharp decline in the number of cases of AA amyloidosis in developed countries. It most commonly affects the kidneys, liver and spleen.
- Hereditary amyloidosis (familial amyloidosis). This inherited disorder often affects the nerves, heart and kidneys. It most commonly happens when a protein made by your liver is abnormal. This protein is called transthyretin (TTR).
- Wild-type amyloidosis. This variety of amyloidosis occurs when the TTR protein made by the liver is normal but produces amyloid for unknown reasons. Formerly known as senile systemic amyloidosis, wild-type amyloidosis tends to affect men over age 70 and typically targets the heart. It can also cause carpal tunnel syndrome.
- Localized amyloidosis. This type of amyloidosis often has a better prognosis than the varieties that affect multiple organ systems. Typical sites for localized amyloidosis include the bladder, skin, throat or lungs. Correct diagnosis is important so that treatments that affect the entire body can be avoided.
Risk factors
Factors that increase your risk of amyloidosis include:
- Age. Most people diagnosed with amyloidosis are between ages 60 and 70, although earlier onset occurs in some cases.
- Sex. Amyloidosis occurs more commonly in men than women.
- Other diseases. Having a chronic infectious or inflammatory disease increases your risk of an AA amyloidosis types condition.
- Family history. Some types of amyloidosis are hereditary or congenital.
- Kidney dialysis. Dialysis can’t always remove large proteins from the blood and amyloidosis. If you’re on dialysis, abnormal proteins can build up in your blood and eventually be deposited in tissue. This condition is less common with more than modern dialysis techniques.
- Race. People of African people appear to be at higher risk of carrying a genetic mutation associated with a type of amyloidosis that can harm the heart.
Symptoms
You may not experience symptoms of amyloidosis until the condition is advanced. When signs and symptoms depend on which of your organs are affected.
Signs and symptoms of amyloidosis may include:
- Symptoms include abnormal heart rhythm, fatigue, numbness of hands or feet, shortness of breath, hoarseness or changing voice, and joint pain.
- Swelling of your ankles and legs
- Severe fatigue and weakness
- Shortness of breath with minimal exertion
- Unable to lie flat in bed due to shortness of breath
- Numbness, tingling or pain in your hands or feet, especially pain in your wrist (carpal tunnel syndrome)
- Diarrhea, possibly with blood, or constipation
- Unintentional weight loss of more than 10 pounds (4.5 kilograms)
- An enlarged tongue, which sometimes looks rippled around its edge
- Skin changes, such as thickening or easy bruising, and purplish patches around the eyes
- An irregular heartbeat
- Difficulty swallowing
When to see a doctor
See your doctor if you persistently experience any of the signs or symptoms associated with amyloidosis.
Treatment
In amyloidosis, the treatment depends on the underlying disease. It is important to control the chronic infection or inflammatory disease which is responsible for the amyloid. Both surgery and medication can be used to successful treatment outcomes for patients.
Comprehensive information on medical treatment options for amyloidosis AA based on the underlying inflammatory disease or infection.
If it affectss kidney transplant is an important option in patients with amyloidosis AA in which stable control of the underlying disease has been achieved. However, appropriate patient selection is strongly recommended due to a higher incidence of heart failure and infections in AA individuals.[rx]
Currently, there is a clinical study on the safety and effectiveness of the medication in preventing the decline of renal function in patients with amyloidosis AA. CLICK HERE to learn more about this study including the six study locations within the United States.
The treatment of AL (historically known as primary) amyloidosis is usually chemotherapy. Decisions about treatment are individualized for each patient depending on the degree of involvement, eligibility for certain protocols, and patient wishes.
For a number of years melphalan (also known as Alkeran), a type of chemotherapy has been the treatment of choice. It is given intravenously or in pill form. Intravenous melphalan followed by a stem cell transplant of the patient’s own (“autologous”), previously collected peripheral blood stem cells is recommended for some patients. Stem cells are cells in the bone marrow from which all blood cells develop. This treatment aims to eliminate the faulty plasma cells which make the amyloidogenic light chains. This will help to recreate a healthy bone marrow and hopefully stop further production of the amyloidogenic light chain protein. This aggressive therapy is part of an ongoing clinical trial within the Amyloidosis Center at Boston Medical Center. Previous treatment with the pill form of melphalan does not necessarily make a patient ineligible for other treatments.
Melphalan in pill form alone or in combination with the steroid dexamethasone may be recommended for some patients and is also effective.
Immunomodulatory drugs (lenalidomide and pomalidomide) and Proteosome inhibitors (bortezomib, carfilzomib and ixazomib) for the treatment of AL amyloidosis are being developed and have been studied in clinical trials here at the center. At present, clinical trials are ongoing with monoclonal antibodies called daratumumab and isatuximab. Both have been used with success in multiple myeloma.
In AA (historically known as secondary) amyloidosis, the treatment depends on the underlying disease. It is important to control the chronic infection or inflammatory disease which is responsible for amyloid formation. Medical or surgical treatment may be used to accomplish this. In addition, colchicine is sometimes prescribed.
For hereditary ATTR amyloidosis, the treatment has been liver transplantation. Since the transthyretin protein which causes hereditary amyloidosis is made in the liver, replacing this organ removes the source of mutant protein production. A new liver will make only normal transthyretin. In 2018, 3 large clinical trials of 3 new pharmaceuticals were published in the prestigious New England Journal of Medicine each showing benefit in ATTR amyloidosis. Again, physician scientists and patients at the BU Amyloidosis Center participated in each of these trials. Data from these trials were sufficient to permit FDA to approve both patisaran or OnpattroTM (Alnylam Pharmaceuticals) and inotersen or TegsediTM (Ionis/Akcea Therapeutics) as the first treatments for ATTR amyloidosis. Both drugs were approved for hereditary ATTR (hATTR or ATTRm) amyloidosis with evidence of neuropathy. While at our Center we utilize the oral drug diflunisal as a means to slow ATTR amyloidosis progression, this drug, while effective and inexpensive, is not tolerated by many patients. We await FDA action on the 3rd new drug reported in 2018, tafamidis (VyndaqelTM, Pfizer, Inc.) which will seek approval for ATTR amyloidosis with cardiomyopathy and provide needed treatment for these patients.
ATTR- wild type (historically known as senile/age related) amyloidosis is quite common and is related to normal transthyretin protein, which misfolds and causes amyloid cardiomyopathy. Early detection and supportive treatment are currently being used. We also use diflunisal, EGCG (green tea extract) and clinical trials for the treatment of this type of amyloidosis.
Supportive Treatments
Supportive treatments are the measures taken to alleviate specific problems and symptoms caused by amyloid deposits in various organs and they are very important in all amyloid types. For example, if the heart or kidneys are affected, patients may need to take a diuretic (water excretion pill), restrict the amount of salt in their diet, or wear elastic stockings and elevate their legs to help lessen the amount of swelling. When the gastrointestinal tract is involved, dietary changes and certain medications can be tried to help symptoms of diarrhea and stomach fullness. These and other supportive therapies have increased the length and quality of life for many individuals with amyloidosis.
Complications
The potential complications of amyloidosis depend on which organs the amyloid deposits affect. Amyloidosis can seriously damage your:
- Heart. Amyloid reduces your heart’s ability to fill with blood between heartbeats. Less blood is pumped with each beat, and you may experience shortness of breath. If amyloidosis affects your heart’s electrical system, your heart rhythm may be disturbed. Amyloid-related heart problems can become life-threatening.
- Kidneys. Amyloid can harm the kidneys’ filtering system, causing protein to leak from your blood into your urine. The kidneys’ ability to remove waste products from your body is lowered, which may eventually lead to kidney failure and the need for dialysis.
- Nervous system. You may experience pain, numbness or tingling of your fingers or numbness, lack of feeling or a burning sensation in your toes or the soles of your feet. If amyloid affects the nerves that control your bowel function, you may experience periods of alternating constipation and diarrhea. If it affects the nerves that control blood pressure, you may feel faint after standing up too quickly.
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