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). Amyloidosis can affect many organs, so care often involves specialists from several fields. At Penn Medicine, hematologists work closely with experts in cardiology, nephrology, neurology, gastroenterology, and other specialties to coordinate your care. Throughout diagnosis and treatment, your team monitors your progress, adjusts treatment as needed, and helps you manage symptoms.

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 often affects the heart and kidneys.

Autoimmune amyloidosis (AA), also called "inflammatory amyloidosis" or "secondary amyloidosis," is associated with 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 (cardiac amyloidosis), 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 the transthyretin gene (ATTR-mutated) can be passed down in families. It is more common in certain ethnic and geographic groups, including people of Black (West African) descent, Portuguese, and Swedes, among others. This inherited form most commonly affects the heart and nerves. Normal or transthyretin (ATTR-wild type) can also cause amyloidosis, but it is an acquired, age-related condition rather than an inherited genetic trait.
• 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.

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

If organ transplantation becomes necessary to replace a heart, liver, or kidney damaged by amyloidosis, the Penn Transplant Institute is a national leader in the field. With more than six decades of transplant experience, we’ve helped pioneer techniques used in transplant programs across the country. We’re the largest transplant center in the region, and our partnership with Children’s Hospital of Philadelphia (CHOP) means seamless care if a younger family member is ever affected.