Amyloidosis is a rare disease affecting about 3,000 patients in the United States each year. Although amyloidosis may be associated with blood cancers such as multiple myeloma, it is not a cancer itself. Amyloidosis results from the buildup of an abnormal protein called amyloid. The amyloid protein accumulates in tissues and organs. This accumulation of the amyloid protein can cause symptoms and organ damage affecting how the heart, kidneys, liver, spleen, nervous system, and gastrointestinal tract work.
The severity of amyloidosis largely depends on which organs are affected and how much amyloid has accumulated. The most life-threatening cases occur in patients with amyloid deposits in the heart.
Amyloidosis can be difficult to diagnose because the symptoms often mimic those of other conditions. Although it is very uncommon, it is likely underdiagnosed. Patients often visit many doctors before finding the cause of their illness. Physicians at Columbia Cancer place a high priority on diagnosing and treating patients in the early stage of the disease before organs are seriously affected.
To diagnose this complex disease, doctors typically begin with a physical exam followed by blood and urine tests. If abnormal proteins are detected in the blood or urine, the next step is a tissue biopsy.
Pathologists evaluate these tissue samples with special staining and mass spectrometry analysis. Usually biopsies are conducted in an outpatient setting.
Samples may be taken from the patient’s abdominal fat or bone marrow. The abdominal fat pad biopsy involves numbing the skin and the fat underneath with a numbing medicine. A needle is then inserted through the skin and into the fat pad underneath. A small piece of fat is removed with the needle. The tissue sample is then examined by a pathologist for abnormal plasma cells or amyloid deposits.
Occasionally, a biopsy may need to be taken from the heart, liver, or kidney to help pinpoint the specific organ affected. For example, if a patient has heart failure then a cardiologist would biopsy the heart, but if a patient has renal failure then a nephrologist would biopsy the kidney.
Because amyloidosis can affect so many different organs, it is critical to have a multidisciplinary team with specialized experience in all of the different organ systems. At Columbia, we bring together experts in many different fields to consult with the patient during a single appointment, thereby minimizing the number of hospital visits needed.
Our pathologists employ the latest technology to evaluate biopsy samples, including dual immunostaining, congo red staining, and computer image analysis. The increased sensitivity of this testing platform allows us to make a definitive diagnosis of amyloidosis—often when other centers have deemed a biopsy negative—and helps us to determine the appropriate therapy.
For a patient with rapidly progressive amyloidosis or one who has visited countless specialists, a definitive diagnosis and immediate treatment can be life-saving.
Amyloidosis is classified into four major types:
• Primary amyloidosis (AL) is the most common form and results from the abnormal production of light chain proteins, which are a part of antibodies. These light chains are produced by blood cells called plasma cells. The light chains can also be increased in multiple myeloma but they do not usually accumulate in tissues as in amyloidosis.
• Secondary amyloidosis (AA) results from the accumulation of serum amyloid protein A as a complication of chronic inflammatory diseases such as familial Mediterranean fever (FMF) or rheumatoid arthritis.
• Familial amyloidosis occurs due to genetic mutations in proteins that lead to the formation of amyloid fibrils. This type of amyloidosis is inherited. The most common form of familial amyloidosis is caused by a mutation in the transthyretin protein (ATTR).
• Senile amyloidosis, also called “wild type” amyloidosis, is caused by an accumulation of normal unmutated transthyretin protein that occurs with aging and especially affects the heart. As the population ages, experts note that TTR cardiac amyloidosis has become more commonplace.
• Localized amyloidosis is an accumulation that occurs in areas such as the larynx or the skin and usually does not need systemic therapy
Certain risk factors may predispose patients to primary amyloidosis, including older age and a previous diagnosis of another blood disease called MGUS or multiple myeloma.
Patients with a chronic infectious or inflammatory disease may be at greater risk of developing secondary amyloidosis.
Patients with a family history of this condition are at greatest risk of developing familial amyloidosis.
Amyloidosis symptoms vary depending on the organ that is affected and how much protein has built up in that area. Since one or several organs may be affected symptoms may vary widely, and seem vague or general at first. Often it takes a team of specialists to diagnose this illness. Since this is a rapidly progressing disease, time is of the essence—it is important to begin treatment as soon as possible.
- When the kidneys are affected, patients may report foamy urine. A physician will order a urine test to find out if amyloid protein has accumulated in the urine.
- When the nervous system is affected, patients may develop numbness, tingling, or weakness in the arms or legs. Carpal tunnel syndrome may also occur. Very often patients experience a change or loss of taste as well as low blood pressure and dizziness when changing the positions.
- When there is abnormal accumulation of amyloid protein in the heart, patients may experience shortness of breath, dizziness, irregular heartbeat, or edema—swelling of the ankles and legs.
- If amyloid has accumulated in the gastrointestinal system, patients may have heartburn (gastrointestinal reflux disease, or GERD), difficulty swallowing, bleeding, diarrhea, constipation, and, a hallmark symptom, swelling of the tongue (macroglosia).
- Other symptoms may include unexplained weight loss, severe fatigue, skin thickening, easy bruising, or purpura—purple patches around the eyes.