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, our providers work closely with experts across specialties to coordinate your care. Throughout diagnosis and treatment, your team monitors your progress, adjusts treatment as needed, and helps you manage symptoms.

Your doctor determines which kind of amyloidosis you have based on the type of protein that builds up in your body. Some types of amyloidosis may be more likely to affect certain organs, like your heart (cardiac amyloidosis) or kidneys (renal amyloidosis). Amyloid can also accumulate in your liver, gastrointestinal tract, nervous system, skin, soft tissue, and other areas.

• AL amyloidosis (immunoglobulin light chain amyloidosis): Formerly known as primary amyloidosis, this is the most common form of the disease. It most often affects the heart, kidneys, and nerves.
• Autoimmune amyloidosis (AA): Also called inflammatory amyloidosis or secondary amyloidosis, AA is associated with chronic infections or inflammatory diseases. These include rheumatoid arthritis, inflammatory bowel disease, and familial Mediterranean fever. AA often affects the kidney.
• Transthyretin amyloidosis (ATTR): Wild-type ATTR occurs when amyloid builds up for unknown reasons, usually in the heart. Hereditary ATTR (hATTR) is passed down from a family member and leads to a mutated TTR protein that typically affects the heart and nervous system.
• Other hereditary amyloidosis: Very rare types of amyloidosis include apolipoprotein amyloidosis (AApoA), hereditary gelsolin (AGel), hereditary fibrinogen (AFib), hereditary lysozyme (ALys), and others. They’re 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

Amyloidosis arises from proteins that transform into amyloid. One of more than 30 known proteins can cause amyloid to build up and impact your health. What causes this to happen may be unknown, like in wild-type ATTR. In other forms of amyloidosis, this can happen due to:

• Changes in your bone marrow plasma cells: Bone marrow plasma cells can secrete the protein that forms amyloid in AL amyloidosis.
• A change in your transthyretin gene: A mutated form of the transthyretin (TTR) gene makes TTR protein accumulate in the body as amyloid. When this gene is passed down in families, it causes hereditary ATTR. It’s more common in certain ethnic and geographic groups, including people from West Africa, Portugal, and Sweden. Genetic testing can check for the gene mutation.
• Chronic infectious or inflammatory diseases: Tuberculosis, rheumatoid arthritis, periodic fever syndromes, and other conditions may result in production of the serum amyloid A protein. This is the common cause of AA.

An early diagnosis and treatment of amyloidosis can help protect your organ and nerve function. Penn Medicine brings together the expertise of specialists from multiple areas to diagnose and treat all types of amyloidosis. 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.