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Key Features

Essentials of Diagnosis

  • Congo red–positive amyloid protein on tissue biopsy

  • Primary amyloid protein is kappa or lambda immunoglobulin light chain

  • Serum or urine (or both) light chain paraprotein

General Considerations

  • A rare condition whereby a protein abnormally deposits in tissue resulting in organ dysfunction

  • There are six main categories, classified according to the type of amyloid protein deposited

    • Primary (immunoglobulin light chain [AL])

    • Secondary (serum protein A, produced in inflammatory conditions [AA])

    • Hereditary (mutated transthyretin [TTR]

    • Senile (wild-type TTR; atrial natriuretic peptide)

    • Renal failure type2-microglobulin, not filtered out by dialysis membranes [Aβ2M])

    • LECT2 (associated with Latino patients)

  • Amyloidosis is further classified as localized (amyloid deposits only in a single tissue type or organ) or, most common, systemic (widespread amyloid deposition)

Clinical Findings

Symptoms and Signs

  • Localized amyloidosis: symptoms and signs are related to the affected single organ, such as hoarseness (vocal cords) or proptosis and visual disturbance (orbits)

  • Systemic amyloidosis: symptoms and signs of unexplained medical syndromes, including

    • Heart failure (infiltrative/restrictive cardiomyopathy)

    • Nephrotic syndrome

    • Malabsorption and weight loss

    • Hepatic dysfunction

    • Autonomic insufficiency

    • Carpal tunnel syndrome (often bilateral)

    • Sensorimotor peripheral neuropathy

  • Enlarged tongue

  • Waxy, rough plaques on skin

  • Contusions (including the periorbital areas)

  • Cough or dyspnea

  • Disturbed deglutition

Differential Diagnosis

  • Plasma cell myeloma

  • Monoclonal gammopathy of unknown significance (MGUS)

  • Other malignant lymphoproliferative disorders

  • Hemochromatosis

  • Sarcoidosis

  • Waldenström macroglobulinemia

  • Metastatic cancer

  • Other causes of nephrotic syndrome, eg, lupus nephritis

Diagnosis

Laboratory Tests

  • Analysis of the serum and urine will reveal a kappa or lambda light chain paraprotein by protein electrophoresis (PEP), immunofixation electrophoresis (IFE), or free light chain assay

  • Mass spectroscopy demonstrates light chain in the tissue biopsy

  • Albuminuria is present with renal amyloid; can be in the nephrotic range

Diagnostic Procedures

  • Echocardiogram

    • Infiltrative cardiomyopathy with thick ventricular walls

    • Unique speckling pattern may be seen

  • ECG: low QRS voltages

  • Blind aspiration of the abdominal fat pad

    • Reveals amyloid two-thirds of the time

    • If unrevealing, then the affected organ needs biopsy

  • Tissue biopsy

    • Demonstrates deposition of a pink interstitial substance in the tissue with the H&E stain

    • Protein stains red with Congo red

    • Becomes an apple-green color when the light is polarized

  • Electron microscopy

    • Amyloid fibrils form beta-pleated sheets

    • Amyloid protein is either the kappa or lambda immunoglobulin light chain

Treatment

Medications

  • Active agents include melphalan, cyclophosphamide, dexamethasone, lenalidomide, and bortezomib

  • See Table 39–3

Table 39–3.Common chemotherapeutic agents.1

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