Amyloidosis
Amyloidosis is extracellular deposition of misfolded protein fibrils that stain apple-green with Congo red under polarized light, most often AL (clonal light chains, linked to plasma cell dyscrasias), AA (chronic inflammation), or ATTR (transthyretin, hereditary or wild-type). Diagnosis requires tissue biopsy for Congo red birefringence plus typing of the amyloid protein, and treatment targets the underlying source, plasma-cell-directed therapy for AL, inflammatory disease control for AA, and transthyretin stabilizers or silencers for ATTR.
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What this article covers
- Overview
Definition: amyloidosis is a group of disorders defined by extracellular deposition of misfolded, low-molecular-weight proteins arranged in a beta-pleated sheet configuration, which infiltrate and…
- Epidemiology
AL amyloidosis: the most common systemic form (about 90% of US cases), arising from a clonal plasma cell dyscrasia; occurs with MGUS, smoldering or symptomatic multiple myeloma, or rarely Waldenstrom macroglobulinemia.
- Risk factors
Underlying clonal plasma cell disorder (AL): MGUS or multiple myeloma is the substrate that generates the amyloidogenic light chain clone.
- Pathophysiology
Protein misfolding: a normally soluble precursor, a monoclonal light chain, serum amyloid A, transthyretin, or beta-2 microglobulin, misfolds into an insoluble beta-pleated sheet configuration.
- Clinical features
Nephrotic-range proteinuria: anasarca, lower extremity edema, and foamy urine from glomerular deposition, the most common presenting manifestation of AL amyloidosis.
- Differential diagnosis
Multiple myeloma without amyloidosis: CRAB features (hypercalcemia, renal failure, anemia, lytic bone lesions) and marrow plasmacytosis of 10% or more, without Congo red birefringence; the two…
- Diagnosis
Confirm with tissue biopsy showing apple-green birefringence under polarized light with Congo red staining; this is the diagnostic gold standard for all types.
- Management
First, type the amyloid and identify the source, because therapy is determined entirely by type, not by organ manifestations alone.
- Complications
Progressive heart failure and fatal arrhythmia: the leading cause of death across amyloid types and the single strongest predictor of survival.
- Prognosis
Cardiac involvement is the dominant prognostic factor: survival in AL amyloidosis ranges from nearly 8 years with minimal cardiac involvement to only about 6 months with advanced disease; NT-proBNP…
- Prevention
Early recognition in at-risk populations: screen with SPEP/UPEP and serum free light chains in any patient with unexplained nephrotic-range proteinuria, unexplained restrictive cardiomyopathy or…
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