Pathogenesis

The factors associated with the pathogenesis of AA amyloidosis include the overproduction of HDL-associated SAA and lipid free SAA, cleavage of SAA to AA, and intracellular proteolysis resulting in the release of amyloidogenic peptides.5 

Secondary Amyloidosis Causes

AS is a well-established cause of reactive amyloidosis.Environmental and genetic factors, including SAA polymorphisms, can determine susceptibility to AA amyloidosis in various rheumatic diseases.3

Differential Diagnosis

1.  AL (primary) amyloidosis results from the tissue deposition of fragments of monoclonal immunoglobulin light chains. In primary amyloidosis, plasma cells proliferate leading to the presence of serum paraproteins.2

2. Hereditary amyloidosis resulting from specific gene mutations in several proteins.6

3. Dialysis-related amyloidosis in patients with end state renal disease due to deposition of beta-2 microglobulin derived fibrils.7

4. Organ-specific amyloidosis (non-systemic)


Light micrograph of a glomerular and vascular amyloid in the kidney. The amyloid accumulates in the tissue forming deposits (dark areas). The deposits can arise from several diseases, or from a primary immune system disorder. Credit: Biophoto Associates / Science Source 

Diagnosis Confirmation

Tissue biopsy is necessary to confirm the presence of amyloid. Laboratory testing may be needed to exclude other conditions, including those listed in the differential diagnosis above. The abdominal fat pad is a  safe and  sensitive site for initial biopsy.8

Amyloid found on the tissue biopsy should indicate further immunofluorescence or immunohistochemical staining for serum amyloid A protein and for kappa and lambda light chains. Absence of staining for lambda or kappa light chains further helps to distinguish AA from AL amyloidosis.9

Renal biopsy may be indicated when the etiology of persistent nephrotic-range proteinuria is in doubt in order to guide management decisions, or if results from the abdominal fat pad biopsy are indeterminate.  

Percutaneous renal biopsy is generally contraindicated in the the setting of uncorrected bleeding diathesis, uncontrolled severe hypertension, hydronephrosis, active renal or perirenal infection, or renal tumor.10

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