Amyloidosis is a group of rare diseases caused by the accumulation of clumps of misfolded proteins, called amyloid fibrils, in organs and tissues in the body. This can happen almost anywhere, from the heart to the brain to the liver to the skin, to name a few. The buildup of amyloid fibrils can change the structure of those organs and tissues, which, in turn, affects their ability to function normally. Without treatment, amyloidosis can result in organ failure and depending on the organs involved, it can be lethal.

To understand this condition, it’s important to know the role proteins play in keeping you healthy. Your body contains tens of thousands of proteins, each tasked with carrying out a particular job that helps the body function properly. But something may go wrong with one of these proteins, affecting its shape. When this happens, the protein is said to have “misfolded.”

Normally, when a protein misfolds, the body has built-in mechanisms to break down and clear away these proteins. But if this doesn’t happen, the misfolded proteins go on to cause problems in the body. The resulting diseases, including amyloidosis, are sometimes referred to as “protein misfolding diseases.”

Fortunately, treatments are available that can relieve symptoms, resolve complications, and treat the underlying problem.

The different types of amyloidosis are classified according to the abnormal protein involved. But doctors also classify amyloidosis according to whether it is spread throughout the body (systemic, affecting more than one tissue or organ) or affects just one organ or tissue (localized).

The most common forms of amyloidosis are described below. The “A” in the name of each condition stands for “amyloid,” while the letter or letters that follow refer to the protein involved.

Systemic types of amyloidosis:

• AL amyloidosis (amyloid light-chain amyloidosis), which is caused by the overproduction and misfolding of “light-chain” proteins, which are components of antibodies or immunoglobulins produced by a type of white blood cell called plasma cells found in the bone marrow.
  
  Light chain-derived amyloid fibrils can deposit and accumulate in nearly any organ in the body, but they most commonly affect the heart and kidneys. In many cases, other organs and tissues are involved, including the peripheral nerves in the arms (causing carpal tunnel syndrome) and legs, as well as the liver, skin, and gastrointestinal tract.
  
  AL amyloidosis is acquired, not inherited. It is usually diagnosed in people over the age of 50. If untreated, the disease can progress rapidly, and depending on the extent of heart involvement, AL amyloidosis can be lethal within a year of diagnosis.

• ATTR amyloidosis (amyloid transthyretin amyloidosis). This occurs when transthyretin (a protein mainly produced in the liver) misfolds, forms amyloid fibrils, and builds up in other organs and tissues. There are two types of ATTR amyloidosis: an acquired form known as wild-type ATTR amyloidosis (wtATTR amyloidosis), and a hereditary form called hereditary ATTR amyloidosis (hATTR amyloidosis).
  
  ATTR amyloidosis can affect the heart, peripheral nerves in the feet, hands, and limbs (i.e., it can cause carpal tunnel syndrome), as well as the autonomic nervous system, which can impair the function of the bladder, digestive system, and genitals.
  
  wtATTR typically occurs in people over 70 and is far more common in men than in women. The inherited form of the disease can be caused by several distinct mutations.
  
  Depending on the mutation involved, hATTR can occur in people in their teens and 20s, though other forms are typically diagnosed in people over 50 years of age.
  
  
• AA amyloidosis (serum amyloid A amyloidosis). This form of amyloidosis affects people who have long-term inflammatory conditions, such as rheumatoid arthritis or Crohn’s disease, or certain chronic infections, such as tuberculosis or osteomyelitis. Only a very small fraction of people with these conditions will develop AA amyloidosis.
  
  In AA amyloidosis, a protein called serum amyloid A, which is produced in the liver, misfolds, forms amyloid fibrils, and deposits and builds up in certain organs—in particular, the kidney and liver.
  
  AA amyloidosis can affect people at any age, and it is the most common form of amyloidosis in children.          

Localized amyloidosis. Sometimes referred to as “organ-specific amyloidosis,” localized amyloidosis affects a single organ. It can occur in just about any organ or tissue in the body, though it commonly affects the skin, bladder, eyes, respiratory system, or central nervous system. Alzheimer’s disease, which is characterized by amyloid plaques in the brain, is perhaps the most well-known type of localized amyloidosis.

Because there are many types of amyloidosis and because the disease can affect nearly any organ and tissue in the body, the list of possible symptoms is long and varied. (Many of these symptoms are also associated with other issues.) Some common symptoms, arranged by the organ involved, include:

• Kidneys. Foamy urine indicative of the presence of protein in urine (proteinuria); swelling in legs, feet, lower abdomen (edema); fatigue; reduced appetite; reduced urine output
• Heart. Swollen legs, irregular heartbeat (arrhythmia), swollen abdomen, fatigue, shortness of breath during physical activity and/or while lying down
• Liver. Abdominal pain, abdominal swelling, reduced appetite, nausea
• Nervous system. Numbness, pain, tingling and/or weakness in limbs, hands, and/or feet, carpal tunnel syndrome, dizziness or lightheadedness when changing positions, nausea, diarrhea, erectile dysfunction, sweating
• Gastrointestinal tract. Gastrointestinal bleeding, constipation, diarrhea, abdominal pain, weight loss
• Skin/soft tissues. Easy bruising, red or purple ring around the eyes, sometimes called “racoon eyes,” macroglossia (thick tongue)
• Lungs and respiratory system. Shortness of breath, wheezing

Because some forms of amyloidosis can affect more than one organ or tissue at the same time, some people may experience symptoms related to more than one organ or tissue. And some people may not experience any symptoms.

Diagnosis of amyloidosis usually begins with a medical history and physical exam. The doctor will ask about symptoms and family history of amyloidosis and other medical conditions.

Depending on the type of amyloidosis suspected, diagnosis may require a tissue biopsy. During this test, a doctor removes a small tissue sample from abdominal fat and/or one or more of the affected organs, such as the heart, liver, or bone marrow. A pathologist will analyze the tissue sample to determine whether amyloid deposits are present. If deposits are found, additional tests are conducted to determine the specific protein involved. Genetic testing may also be ordered.

It’s important to determine which organs are involved in the disease, so bloodwork and/or a urine sample may be needed to assess the function of various organs. If a doctor suspects that a particular organ is involved, he or she may order one or more imaging studies such as an ultrasound, X-ray, or MRI. 

Other tests may be required to determine which organs are involved. For example, if the doctor suspects cardiac involvement, an electrocardiogram (known as an ECG or EKG), an echocardiogram, or cardiac MRI may be used to evaluate heart function. If other organ involvement is suspected, the doctor will order organ-specific functionality tests.

Treatment of amyloidosis varies depending on the protein involved, whether the amyloidosis is systemic or localized, the severity of disease, which organs and/or tissues are involved, the age and overall health of the patient, and several other factors.

Specific treatment options will be based on each of these variables, but below are some common approaches:

Managing symptoms and complications. Various medications, lifestyle modifications, and other therapies can help reduce and relieve symptoms and complications caused by amyloidosis. As an example, a patient with cardiac amyloidosis may be given diuretics (water pills) and placed on a low-salt diet to help reduce swelling in the abdomen and legs, and depending on symptoms, a pacemaker may be implanted to regulate heart rate. Sometimes amyloidosis causes organ failure or severe organ damage. In these cases, organ transplantation (heart, liver, kidney, etc.) may be necessary.

Treating the underlying cause of amyloidosis. There are also therapies to treat the underlying cause of amyloidosis. The specifics vary according to the protein involved but may include:

• Chemotherapy. Chemotherapy medications work by destroying abnormal cells. In addition to cancer, they are also used to treat some forms of amyloidosis—in particular AL amyloidosis. The medication destroys plasma cells in the bone marrow that produce the light-chain proteins that give rise to AL amyloidosis. Because fewer light-chain proteins are produced, this reduces the number of amyloid fibrils. After chemotherapy, patients may be given an autologous stem cell transplantation.
  
• Medications that stabilize proteins. Because amyloidosis is caused by misfolded proteins, this approach stabilizes proteins so that they are less likely to misfold, and thus less likely to clump together into amyloid fibrils. Tafamidis, a medication used to treat ATTR amyloidosis, for instance, stabilizes the transthyretin protein and prevents it from misfolding.
  
• Treating inflammatory disease and infections. AA amyloidosis occurs in people who have certain chronic inflammatory diseases and long-term infections. Treatment of this form of amyloidosis typically uses therapies that reduce inflammation and clear infections.
  
• Medications that reduce levels of abnormal proteins. Some medications reduce the production of proteins that can cause amyloidosis. For example, two medications, patisiran and inoteseren, can reduce the production of the transthyretin protein that is involved in ATTR amyloidosis.

The prognosis for people with amyloidosis can vary greatly depending on the type of amyloidosis, age and overall health, and the organs and tissues involved. In general, localized amyloidosis has a better prognosis than systemic forms of the disease.

Because early diagnosis and treatment can substantially improve outcomes, it’s important to talk to your doctor if you suspect you may have amyloidosis.