Last updated: November 6, 2014
ICD-9 Code: 277.3
ICD-10 Code: E85
Definition: Amyloidosis is a multisystem disorder caused by deposition of fibrillar protein aggregates that interfere with structural integrity and function of targeted organs or tissues. Four major forms are distinguished by the deposited protein and the clinical associations (Table 1).
Etiology: Primary amyloidosis is commonly associated with plasma cell dyscrasias such as multiple myeloma or may be seen with other malignancies such as medullary carcinoma of the thyroid. Secondary amyloidosis occurs most commonly in association with inflammatory syndromes such as FMF or RA. 132-Microglobulin amyloidosis occurs in association with hemodialysis.
Pathology: The various proteins associated with amyloidosis all show a characteristic fibrillary array, most clearly seen by electron microscopy. Under the light microscope, amyloid deposits are visualized by staining with Congo red. When viewed under polarized light, the stained fibers show a characteristic apple-green birefringence.
Table 1 Syndrome of Systemic AmyloidosisTypeClinical SyndromesProtein B2-MicroglobulinHemodialysis AssociatedB2-Microglobulin
|Immunoglobulin (AL)||Primary, Myeloma- associated amyloidosis||lg light chains|
|Hereditary||Familial||Various non-lg proteins|
Demographics: Patients can be of almost any age, from childhood to elderly, depending on the underlying cause. Primary amyloidosis shows a male predominance.
Cardinal Findings: In primary amyloidosis, the most commonly involved organs are the kidney, heart, liver, and skin; skeletal muscle and the tongue may also be affected. Peripheral neuropathies are seen, but the central nervous system (CNS) is generally not involved. Secondary amyloidosis most commonly presents with nephrotic syndrome or gastrointestinal (GI) bleeding. Macroglossia is not seen with secondary amyloidosis. The initial finding in hemodialysis associated amyloid is often CTS.
Uncommon Manifestations: In primary amyloidosis, amyloid deposits may be seen in the synovium and occasionally in the synovial fluid.
Diagnostic Tests: Biopsies of affected tissues are usually required. The tissues are stained with Congo red and viewed under polarized light. Kidney and peripheral nerve biopsy specimens can be useful if there are known abnormalities in these tissues; otherwise, a blind abdominal fat pad aspirate should be attempted.
Keys to Diagnosis: Suspect amyloid in a patient with multisystem disease, especially those with new-onset cardiomyopathy, peripheral neuropathy, renal insufficiency, or nephrotic syndrome. Biopsy demonstration of amyloid deposits is diagnostic.
Therapy: In primary amyloidosis, chemotherapy with melphalan and prednisone is usually recommended, although it is not clear that this treatment prolongs survival. Cardiomyopathy is especially resistant to medical therapy. In secondary amyloidosis, treatment should be directed at controlling the underlying inflammatory process. Colchicine has some utility in patients with amyloid secondary to FMF. Recent uncontrolled studies have shown the benefit of TNF inhibitors in patients with amyloidosis and in those with primary and secondary amyloidosis.
Surgery: Surgery is not generally indicated. Organ transplantation (heart, kidney) may be attempted in some cases.
Prognosis: In primary amyloidosis, only 20% of patients are alive 5 years after diagnosis. Disease progression is generally slower in secondary forms, with some patients surviving 10 years after diagnosis.
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