Evaluation of a patient with suspected systemic amyloidosis

SPEP: serum protein electrophoresis; UPEP: urine protein electrophoresis; FLC: free light chain; NT-proBNP: N-terminal pro-brain natriuretic peptide.
* Amyloidosis may be suspected in a patient presenting with one or more of the following:

• Unexplained non-diabetic nephrotic range proteinuria
• Restrictive cardiomyopathy or otherwise unexplained congestive heart failure
• Increased NT-proBNP in the absence of known primary heart disease
• Unexplained edema, hepatosplenomegaly, or carpal tunnel syndrome
• Unexplained facial or neck purpura
• Macroglossia

Suspicion of amyloidosis is increased in patients in whom these findings are present in the setting of chronic poorly controlled systemic autoimmune, autoinflammatory, or infectious disease; an established diagnosis of multiple myeloma, Waldenström macroglobulinemia, or lymphoma; or a family history of amyloidosis.
¶ The presence of amyloid fibrils can be confirmed by:

• Appearance on electron microscopy
• Congo red binding leading to green birefringence under polarized light
• Thioflavine-T binding producing an intense yellow-green fluorescence

Δ Clinical suspicion may remain if the patient has a monoclonal plasma cell proliferative disorder and/or if evaluation for other causes of symptoms is unrevealing.
◊ While mass spectrometry is preferred, immunohistochemical staining (eg, for kappa and lambda light chains, transthyretin, and serum amyloid A component) of the amyloid can determine the type of amyloidosis if performed by a laboratory that has a very high volume of amyloid samples and experience with these techniques.
§ The frequency of organ involvement differs by amyloid type. For diagnostic purposes, it is helpful to differentiate those with primary nerve, kidney, or liver involvement from those with primary cardiac involvement. The evaluation of patients with predominant involvement of other organs is individualized. Cardiac involvement may be suspected in patients with arrhythmia or heart block on electrocardiogram; restrictive cardiomyopathy on echocardiogram; or findings on cardiac magnetic resonance imaging.