• Amyloidosis pathogenesis involves excessive misfolding of native protein (eg, light chains, beta2-microglobulin, transthyretin) due to predisposing mutations or excessive protein production.  This structural change in soluble precursors promotes formation of beta-pleated sheets that polymerize into insoluble fibrils and deposit in tissues causing organ dysfunction.  Amyloid deposits appear as amorphous pink material on light microscopy with apple-green birefringence on Congo red stain under polarized light.
• Serum amyloid A, an acute phase reactant induced by cytokines, is excessively produced during chronic inflammatory states, resulting in AA amyloidosis.  RA is the most common cause, but inflammatory bowel disease, chronic infection (eg, osteomyelitis, tuberculosis), and familial Mediterranean fever are also frequently associated.  AA amyloidosis most commonly affects the kidneys, presenting as nephrotic syndrome.  Hepatomegaly is frequent with splenomegaly occasionally seen.  Cardiac involvement (eg, restrictive cardiomyopathy) is rare.