Amyloidosis
Amyloidosis is a group of diseases characterized by the abnormal deposition of fibrillar proteins, known as amyloid, in various organs of the body. The most common form, AL amyloidosis, occurs when misfolded immunoglobulin light chains produced by malignant plasma cells aggregate, impairing the function of essential organs such as the heart, kidneys, and liver. Certain individuals, particularly men and those with chronic inflammation or long-term dialysis, are at higher risk for developing amyloidosis. Symptoms can vary widely based on the organs affected, with common manifestations including swelling, irregular heartbeat, and peripheral neuropathy.
Diagnosis is typically achieved through tissue biopsies and specialized staining techniques. Treatment often involves chemotherapy regimens similar to those for multiple myeloma, aimed at reducing abnormal plasma cell numbers and managing symptoms. While some patients experience temporary improvement in organ function with treatment, the disease can lead to severe outcomes, including heart disease and renal failure, particularly in cases with cardiac involvement. There is currently no known method to prevent amyloidosis, making awareness and early diagnosis critical for managing the condition.
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Amyloidosis
ALSO KNOWN AS: AL amyloidosis, immunoglobulin light-chain amyloidosis, primary amyloidosis
RELATED CONDITIONS:Multiple myeloma
DEFINITION: Amyloidoses are a class of illnesses in which fibrillar protein deposits form throughout the body. Immunoglobulin-related (AL) amyloidosis, a disorder sometimes caused by cancerous antibody-secreting plasma cells, results when misfolded antibody chains form deposits that impair function of the heart, kidneys, and other organs.
Risk factors: Patients with conditions that cause chronic inflammation or those who receive long-term dialysis are at a higher risk of developing certain amyloidoses, and men are also more likely than women to develop anyloideses.
Etiology and the disease process: In a minority of patients with multiple myeloma, antibody fragments that are produced by malignant plasma cells form insoluble fibrillar protein deposits. Deposits can form in many organs but are most often found in the kidney, heart, liver, and peripheral and autonomous nervous systems. These deposits ultimately lead to death, most commonly via heart disease and renal failure.
Incidence: The overall incidence of AL amyloidosis is approximately 1 in 100,000 people per year. Men make up 70 percent of amyloidosis patients. Approximately 15 percent of patients with multiple myeloma develop AL amyloidosis, but cases of myeloma-associated amyloidosis make up a small fraction of AL amyloidosis cases.
Symptoms: Symptoms depend on the organs involved and vary among patients. Common symptoms include peripheral edema, proteinuria, hepatomegaly, hypotension, shortness of breath, irregular heartbeat, purpura, macroglossia, carpal tunnel syndrome, and peripheral neuropathy.
Screening and diagnosis: Many amyloidoses are diagnosed by Congo Red staining of tissues biopsied from subcutaneous fat pads, rectal mucosa, bone marrow, or other sources. Once diagnosis of amyloidosis is established, a free light chain blood test is performed to confirm immunoglobulin chains as the cause of amyloid deposits.
Treatment and therapy: Current treatments for amyloidosis parallel those used for multiple myeloma but depend on the type of amyloidosis the patient is experiencing. Melphalan plus predisone reduces the number of malignant plasma cells and levels of circulating immunoglobulin light chains. This is often followed by autologous stem cell transplantation, aimed at rebuilding healthy bone marrow. In some patients, treatment results in a temporary resorption of amyloid fibrils and improvement in organ function. The malignant plasma cells are not completely eradicated, however, and remission is the usual course. IDOX (4′-deoxy-4′-iododoxorubicin), a drug that binds to amyloid fibrils and promotes their disassembly, has shown promise in early trials. For transthyretin amyloid cardiomyopathy (ATTR-CM), studies have shown that RNA interference (i) therapy vutrisiran can be an effective treatment option. Chemotherapy is also a potential treatment option.
Prognosis, prevention, and outcomes: Prognosis for patients with AL amyloidosis depends on which organs are affected. Patients with cardiac involvement have the worst prognosis, while patients with involvement limited to other organs have longer median survival times. There is no known way to prevent amyloidosis.
Bibliography
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