Amyloidosis

Posted by Graham McMahon • October 8th, 2010

The latest article in our Clinical Problem-Solving series, “A Heavy Heart,” begins:

A 73-year-old man presented with a 6-month history of progressive, symmetric edema that began in the lower extremities and subsequently involved his thighs, scrotum, and arms. He had dyspnea on exertion, orthopnea, and paroxysmal nocturnal dyspnea, as well as chest pressure on mild exertion. Despite anorexia and early satiety, he gained 16 kg (35 lb) and noted new abdominal distention. He had no abdominal pain, nausea, or vomiting and reported no fevers, chills, night sweats, or urinary changes.

The amyloidoses are a collection of systemic diseases characterized by the extracellular deposition of a proteinaceous material that has characteristic staining properties. Although AL amyloidosis and transthyretin-associated (senile or familial) amyloidosis are the most common forms, secondary (AA) amyloidosis and other rare variants also exist.

Clinical Pearls

What are the characteristics of senile amyloidosis?

Senile amyloidosis, characterized by cardiac deposition of wild-type transthyretin, is typically an indolent disease in older men that is generally restricted to the heart (with the exception of carpal tunnel involvement). In contrast to the indolent nature of cardiovascular involvement in transthyretin-associated amyloidoses, cardiac disease in AL amyloidosis can be rapidly progressive.

What are the characteristics of AL amyloidosis?

AL amyloidosis is a plasma-cell dyscrasia, with monoclonal immunoglobulin light chains forming amyloid-fibril precursors. It can be widespread, involving the autonomic and peripheral nervous systems, the kidneys, and the liver.

Morning Report Questions

Q: How does cardiac involvement affect the prognosis of patients with AL amyloidosis?

A: Clinical cardiac involvement occurs in up to 50% of cases and is a poor prognostic sign, conferring a life expectancy of less than 6 months if left untreated. In contrast to the indolent nature of cardiovascular involvement in transthyretin-associated amyloidoses, cardiac disease in AL amyloidosis can be rapidly progressive; light chains may contribute to the damage through direct toxic effects on the myocardium.

Q: How is AL amyloidosis treated?

A: Chemotherapy may result in a cure or prolong life in patients with AL amyloidosis. In a case series of patients treated with high-dose chemotherapy and autologous stem-cell transplantation, treatment-related mortality was high but approximately 75% of the patients were alive at 1 year, and 40% of these patients had a complete hematologic response. When patients are ineligible this type of treatment, high-dose dexamethasone and melphalan has been reported to result in functional improvement in approximately 50% of patients and in complete remission in 33%.

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