Chapter 72: Amyloidosis

DEFINITION

• Amyloidosis is a clinical syndrome resulting from disorders of secondary protein structure, in which a precursor protein is secreted from the cell in a soluble form, only to become insoluble at some tissue site, ultimately compromising organ function.

• The term amyloid is used to describe a substance with a homogeneous eosinophilic appearance by light microscopy, a green birefringence on polarizing electron microscopy, and a characteristic β-pleated sheet appearance by x-ray diffraction.

• Terms such as primary, secondary, senile, dialysis-associated, and myeloma-associated have been abandoned in favor of the etiologically based, chemical terminology (Table 72–1) (e.g., immunoglobulin light chain amyloidosis is termed AL amyloidosis).

• The incidence of AL amyloidosis is approximately 4.5 per 100,000 persons in the United States.

• Amyloid A (AA) amyloidosis is increasingly rare, occurring in less than 1 percent of persons with chronic inflammatory diseases in the United States and Europe.

• AA amyloidosis is more common in Turkey and the Middle East, where it occurs in association with familial Mediterranean fever.

• AA is the only type of amyloidosis that occurs in children.

• Amyloid β₂-microglobulin (Aβ₂M) amyloidosis usually manifests as deposits in the joint synovial and occurs in patients on long-term dialysis.

  — Aβ₂M amyloidosis is also declining in incidence with changes in dialysis techniques.

• The inherited amyloidoses are rare in the United States, with an estimated incidence of less than approximately 1 per 100,000 persons.

• Amyloidogenic transthyretin (ATTR) amyloidosis is the most common form of familial amyloidosis and is associated with mutations of the gene encoding transthyretin (TTR).