Amyloidosis is not a single disease but a heterogeneous group of diseases that share in common the extracellular deposition of insoluble fibrillar proteins in tissues and organs. These protein deposits derive from diverse and unrelated serum precursor proteins, yet have similar beta-pleated sheet structural conformations. Furthermore, all forms of amyloid display apple-green birefringence when stained with the cotton-wool dye Congo red and viewed under polarized light. Indeed, this observation (via tissue biopsy) remains the primary means of establishing the diagnosis of amyloidosis. Accumulation of amyloid deposits leads to tissue and organ dysfunction, which in turn causes clinical symptoms and, for some patients, death.
Amyloid diseases are classified by the biochemical composition of the serum precursor proteins that form the amyloid fibrils and deposits. Indeed, once amyloid deposition has been identified, it is important to identify the precursor protein because the prognoses and treatments of the various amyloid diseases depend on the underlying cause. To date, more than 20 amyloid fibril precursor proteins and their associated diseases have been identified. Of these, the most common amyloid diseases are (1) primary or immunoglobulin light-chain protein–related (AL) amyloidosis; (2) secondary (AA) amyloidosis associated with chronic inflammatory disease; (3) dialysis-associated β2-microglobulin (β2-m) amyloidosis; and (4) hereditary amyloidosis. Notably, the clinical manifestations of these forms of amyloidosis are not identical (Table 57–1). Hence, each is discussed in detail.
Table 57–1. Organ Systems Commonly Involved Clinically by Various Forms of Amyloidosis. ||Download (.pdf)
Table 57–1. Organ Systems Commonly Involved Clinically by Various Forms of Amyloidosis.
|Organ System||Primary (AL) Amyloidosis||Secondary (AA) Amyloidosis||Dialysis-Associated β2-Microglobulin (β2-m) Amyloidosis||Hereditary Amyloidosisa|
- AL amyloidosis should be suspected in all patients with unexplained heart failure, nephrotic syndrome, neuropathy, and hepatomegaly.
- Approximately 98% of patients with AL amyloidosis have detectable serum or urine monoclonal immunoglobulin light-chain protein. However, this finding alone is insufficient to establish the diagnosis of AL amyloidosis.
- AL amyloid, like all forms of amyloid, displays apple-green birefringence when viewed under polarized light after staining with Congo red.
- Bone marrow examination almost always reveals a monoclonal population of plasma cells.
- Tissue immunohistochemical analysis or protein sequencing by mass spectroscopy is necessary to identify the light-chain origin of AL amyloid fibrils. If inconclusive, other diagnostic testing (eg, ultrastructural fibril characterization) should be done.
AL amyloidosis is a plasma cell dyscrasia associated with multisystem involvement, rapid progression, and short survival. It is a rare disease with an incidence of 8 patients per 1 million persons per year. It usually affects people older than 40 years ...