Amyloidosis

Amyloidosis is a rare and serious disease that occurs when an abnormal protein called amyloid builds up in the body. Amyloid can deposit in organs and tissues throughout the body (systemic), or it can deposit in just one location (localized).

There are a few types of amyloidosis:

Immunoglobulin light chain amyloidosis (AL), formerly known as "primary amyloidosis," is the most common form of amyloidosis. It most commonly affects the heart and kidneys.

Autoimmune amyloidosis (AA), also called "inflammatory amyloidosis" or "secondary amyloidosis," this type is associated with some chronic infections or inflammatory diseases, including familial Mediterranean fever, rheumatoid arthritis and inflammatory bowel disease.

Transthyretin amyloidosis (ATTR) comes in two variants. Wild-type (ATTRwt) is caused by a normal protein that deposits as amyloid for unknown reasons, usually in the heart. Mutant (ATTRm) is inherited and leads to a mutated TTR protein that typically affects the heart and nervous system.

Other hereditary or familial amyloidosis: Very rare types of amyloidosis (AApoAI/II, AGel, AFib, ALys) can be passed down in families and affect a variety of organs.

Amyloidosis is not a type of blood cancer. It is a rare but serious condition that can occur in people with or without blood cancer. AL Amyloidosis is linked with hematological malignancies such as multiple myeloma and lymphoma.

Treatments for AL amyloidosis are similar to treatments for blood cancer. If you have blood cancer and amyloidosis, some of the same treatments can help resolve both and you may work with blood cancer specialists with experience in amyloidosis treatment at our Blood Cancer Program and Amyloidosis and Paraproteinemia Clinic.

The symptoms of amyloidosis depend on where amyloid has deposited. Symptoms might include:

• Diarrhea or constipation
• Enlarged tongue
• Fatigue or weakness
• “Foamy” urine (pee)
• Pain, numbness or tingling in the hands, feet or joints
• Repeat infections
• Skin changes, such as easy bruising or purplish patches
• Trouble swallowing
• Weight loss for no apparent reason

In addition, if amyloidosis affects the heart, you might experience:

• Chest pain
• Irregular heartbeat
• Shortness of breath
• Swollen legs, ankles and feet

Systemic amyloidosis arises from normal or abnormal proteins that transform into amyloid. Although there are over 30 known proteins that cause amyloid in humans, these are the most common causes and the types of amyloidosis that can arise:

• Amyloid production from bone marrow plasma cells: 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. This is the primary cause of light chain amyloidosis (AL).
• Mutation in the transthyretin gene or normal transthyretin: A mutated form of transthyretin gene (ATTR-mutated) or normal transthyretin (ATTR-wild type) 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. This is the primary cause of transthyretin amyloidosis (ATTR).
• Chronic infectious or inflammatory diseases: Diseases such as tuberculosis, rheumatoid arthritis or periodic fever syndromes may result in production of the serum amyloid A protein. The most common organ affected is the kidney. This is the common cause of secondary amyloidosis, autoimmune amyloidosis (AA).

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.

Early and accurate diagnosis of amyloidosis is critical. Diagnostic information guides treatment decisions and helps prevent organ damage, organ failure and death. Tests needed for an amyloidosis diagnosis may include:

• Blood and urine tests to detect the abnormal protein and determine whether your organs are working properly
• Biopsy, during which a healthcare provider takes a small sample of tissue that is examined for amyloid deposits
• Imaging tests to take pictures inside the body at organs and tissues that might be affected
• Echocardiogram, which can detect heart damage

There is no cure for amyloidosis, but treatment can help manage symptoms, protect organs from further damage, and slow or stop amyloid production. 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:

• Eliminate the protein precursor that forms amyloid, which will allow for improvement or stabilization of organ function, or
• Interrupt formation of new amyloid to stabilize organ function from further deterioration.

Treatment is personalized to the type of amyloidosis, its cause and the organs affected. Options may include:

• Bone marrow and stem cell transplantation
• Chemotherapy
• Dialysis to remove waste and excess fluid from the blood when the kidneys aren’t functioning properly
• Heart medications
• Targeted therapy that interferes with the process of amyloid production
• Organ transplantation to replace heart, liver or kidneys that have been severely damaged

Throughout your treatment, Penn Medicine’s expert hematologists work with the other specialists involved in your personalized plan of care. Together, we track your health and progress and adjust treatment as needed. Along the way, our nurses and nurse navigators help coordinate your care and get you whatever support you need.