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INTRODUCTION

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SUMMARY

Amyloidosis should be considered in any patient presenting with nephrotic range proteinuria; infiltrative cardiomyopathy or heart failure with preserved ejection fraction; hepatomegaly without specific imaging findings; or peripheral neuropathy, particularly if a monoclonal protein is present; as well as any patient with atypical multiple myeloma.

When a patient is seen with a relevant syndrome, the patient should have immunofixation of serum and urine proteins and measurement of κ and λ immunoglobulin free light chains. If all of these tests are normal, it is unlikely that the patient has immunoglobulin light-chain (AL) amyloidosis.

If any of the above tests are positive, further investigation for amyloidosis should be undertaken. The diagnostic test of choice is subcutaneous fat aspiration; marrow biopsy is the second best procedure. With these two tests, 83 percent of patients will have a positive result when stained with Congo red under green birefringence.

All patients with biopsy proven amyloidosis should have the deposits analyzed by laser capture microdissection mass spectroscopy to definitively classify the exact protein subunit composing the amyloid. This technique does not distinguish between systemic and localized amyloidosis, however.

The prognosis in AL amyloidosis is determined by three tests: (1) the N-terminal probrain natriuretic peptide, (2) serum troponin, and (3) the difference between the involved and uninvolved immunoglobulin free light chains. These three tests can be combined to stage the patient from stage 1 through stage 4.

Treatment of AL amyloidosis involves either standard systemic chemotherapy or high-dose chemotherapy with autologous stem cell transplantation. Fit patients who are expected to have low morbidity with transplantation should undergo this approach. The majority of patients, however, will not be candidates for transplantation and should be treated with traditional systemic chemotherapy; with the cyclophosphamide, bortezomib, and dexamethasone regimen currently favored by many investigators.

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Acronyms and Abbreviations

CRAB, calcemia, renal insufficiency, anemia, or bone disease; CyBorD, cyclophosphamide, bortezomib, and dexamethasone; MRI, magnetic resonance imaging; NT-ProBNP, N-terminal probrain natriuretic peptide; TTR, transthyretin.

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DEFINITION AND HISTORY

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Amyloidosis is a heterogeneous group of diseases characterized by tissue infiltration with misfolded protein precursors as amyloid material. For nearly 100 years, amyloid has been defined by its staining properties. Divry and Florkin first used Congo red to detect amyloid in the brain of patients with Alzheimer disease.1 Amyloid deposits are always extracellular and, under the light microscope, appear amorphous and pink when seen after standard hematoxylin-and-eosin staining. All amyloid deposits bind Congo red dye and demonstrate green birefringence under polarized light,2 and this test remains the standard diagnostic procedure required to confirm a diagnosis of amyloidosis. Under the electron microscope, amyloid consists of rigid, linear, nonbranching fibrils of 9.5 nm diameter.3 Historically, amyloid was defined based on whether there was a family history (inherited), whether it was the result of a chronic inflammatory condition (secondary), or whether it was idiopathic (primary). Today, amyloidosis is classified based on the protein subunit composition of the deposits. ...

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