Multiple Myeloma and Amyloidosis Conditions, Diagnostics & Treatments

Amyloidosis is a condition in which too much of a particular protein (amyloid) collects in the organs so that they are not able to work normally.

There are numerous types of amyloidosis based upon the type of protein that accumulates and the disease can also be localized or systemic. At the moment, treatment is centered primarily upon stopping the production of the protein that causes the amyloidosis. By doing so, the function of the organs involved will stop getting worse and the body can actually heal itself if the protein production is shut down thoroughly. Fortunately, treatment for many of the types of amyloidosis has improved significantly within the past few years. There are promising drugs as well and on-going active research that should further improve outcomes.

Amyloidosis can affect the heart, kidneys, liver, nervous system, and intestines. For patients with amyloidosis that affects the heart, The condition is rare (affecting fewer than 4,000  people in the United States each year), but it can be fatal. It is often undiagnosed since the symptoms of patients afflicted with amyloidosis mimic so many other diseases. Many patients have symptoms for years before the diagnosis is made, usually by a tissue biopsy.

There are many forms of amyloidosis but the major ones are listed below:

  • AL Amyloidosis
  • ATTR Amyloidosis
  • AA Amyloisdosis
  • Other less common types of Amyloidosis
    • ALec2- Found in people of Mexican heredity and often causing kidney disease and recently discovered. No known therapy exists at the moment.
    • AApoA1- Hereditary variant of the Apo A1 protein.
    • Aβ²Μ – Caused by the accumulation of the normal beta-2 microglobulin protein. This protein typically builds up in patients on dialysis for many years and causes joint swelling and neuropathy. Better dialysis methods or kidney transplantation can correct the problem.

Amyloidosis Diagnosis & Testing

The diagnosis of amyloidosis is often delayed because the symptoms are so varied. Patients often get treated for heart or kidney failure for months before the underlying root of the problem is identified, typically by a biopsy. 

Blood and urine tests may reveal an abnormal immunoglobulin protein in the body in those patients with AL Amyloidosis, but the only way to diagnose amyloidosis for certain is to take a sample of tissue for analysis under a microscope. Tissue is often taken from the fat around the abdomen which can be done on an outpatient basis in patients suspected as having the condition. This fat aspiration test will show a confirmatory positive result in 80% of patients with amyloidosis. Alternatively, a biopsy of the organ that is not functioning properly such as the heart, kidney or nerve can more reliably identify the condition but can be more cumbersome to obtain. This method of identification is becoming more common in our experience and often leads to the diagnosis in patients not suspected of the condition beforehand. A biopsy of the bone marrow is another useful method of detection and is critical to perform in patients suspected as having AL amyloidosis since it can identify and quantify the bone marrow lymphocytes or plasma cells which typically live there and are causing the problem. All of the above samples are stained with a dye called Congo Red that reacts with amyloid which can then be identified under a microscope.

It is critical to characterize the nature of the amyloid protein that is present since each of the various types of amyloidosis (such as AL, ATTR, or AA) is treated quite differently. Mass spectroscopy is a special technique that can be used on tissue samples to reliably determine the type of protein present. Blood samples can be used to sequence the various genes such as transthyretin or fibrinogen to determine if a predisposing gene variant exists. For patients with AL Amyloidosis, the free light chain assay is extremely useful to monitor the response to treatment. Patients suspected of heart involvement can get a cardiac MRI which can typically demonstrate findings suggestive of amyloidosis in those patients afflicted. All of these tests are available at Cedars-Sinai.

Amyloidosis Symptoms & Risk Factors

The cause for amyloid to be produced and to collect in the tissues is not known. The risk of getting amyloidosis is not known to be connected to what a person eats (including how much protein) or does for a living. The risk of developing amyloidosis is greater in people who:

  • Are older than 50
  • Have a chronic infection or inflammatory disease
  • Have a family history of amyloidosis
  • Have multiple myeloma. Between 10 and 15% of people who have multiple myeloma develop amyloidosis.
  • Have a kidney disease that has required dialysis for more than five years

Symptoms vary widely from person to person and depending on which organs are affected. Some people do not even have symptoms, which makes the condition difficult to diagnose. When amyloidosis is associated with another disease, symptoms may be masked.

Symptoms can include:

  • General - Fatigue, loss of weight, weakness
  • Cardiac - Shortness of breath, dizziness or feeling faint, exercise intolerance, irregular heart rate, palpitations
  • Neurologic - Numbness or tingling in the hands or feet, painful feet/legs; carpal tunnel syndrome, which causes pain, numbness or tingling in the fingers. Approximately four out of 10 people with amyloidosis develop this syndrome.
  • Gastrointestinal - Diarrhea alternating with constipation, abdominal cramps, early satiety, nausea and vomiting
  • Kidney - Foam in urine, swelling of the ankles and legs
  • Mouth and throat - Macroglossia (enlarged tongue), difficulty swallowing, hoarse voice
  • Skin – Bruises easily particularly around the eyes

The severity of amyloidosis depends on which organs it affects. It can be life threatening if it causes kidney or heart failure.

If the amyloidosis affects the kidneys, their ability to filter the blood becomes impaired. Protein leaks from the blood into the urine. The loss of protein from the blood can cause fluid to leak out of the blood vessels, resulting in swelling in the feet, ankles and calves. Eventually, there is so much damage to the kidneys that they are not able to remove waste products from the body and they fail.

If amyloidosis affects the heart, the first symptom typically is shortness of breath even with only light activity. Climbing a flight of stairs or walking long distances may be difficult without having to stop. The buildup of amyloid in the heart lessens its ability to fill up with blood between heartbeats. As a result, less blood is pumped with each beat, and the heart is not able to keep up with the body's needs. The buildup of amyloid can also cause problems with the electrical system of the heart, resulting in irregular heartbeats (arrhythmia).

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