Amyloidosis

Essentials of Diagnosis
The diagnosis is based on clinical suspicion, family history, and preexisting long-standing infection or debilitating illness.
Microscopic examination of biopsy (eg, gingival, renal, rectal) or surgical specimens is diagnostic.
Fine-needle biopsy of subcutaneous abdominal fat is a simple and reliable method for diagnosing secondary systemic amyloidosis.
General Considerations
Amyloidosis is a group of disorders manifested by impaired organ function due to infiltration with insoluble protein fibrils. Different fibrils can be correlated with the clinical syndromes. In primary amyloidosis (AL), the protein fibrils are monoclonal immunoglobulin light chains, whereas in secondary amyloidosis (AA), protein deposits are derived from acute phase reactant apolipoprotein precursors. Familial amyloidosis syndromes commonly cause infiltrative neuropathies. Other types of amyloidosis may also be hereditary. Over 20 types of fibrils have been identified in amyloid deposits. Amyloidosis due to deposition of
2-microglobulin in carpal ligaments occurs in long-term hemodialysis patients.
Clinical Findings
SYMPTOMS AND SIGNS
The symptoms and signs of primary amyloidosis are due to amyloid infiltration and subsequent malfunction of the infiltrated organ (eg, nephritic syndrome and renal failure, cardiomyopathy and cardiac conduction defects, Alzheimer's disease, intestinal malabsorption and pseudo-obstruction, carpal tunnel syndrome, macroglossia, peripheral neuropathy, end-organ insufficiency of endocrine glands, respiratory failure, capillary damage with ecchymosis). Secondary amyloidosis is more often limited to the liver, spleen, and adrenals. Familial syndromes commonly cause infiltrative neuropathies.
LABORATORY TESTS
The diagnosis of primary amyloidosis is based on clinical suspicion with corroboration provided by detection of a monoclonal gammopathy on serum protein electrophoresis and microscopic examination of abdominal fat pad aspirates; rectal or gingival biopsies reveal amyloid protein (green birefringence under polarizing microscope after Congo red staining). In systemic disease, rectal or gingival biopsies show a sensitivity of about 80%, bone-marrow biopsy about 50%, and abdominal fat aspiration between 70% and 80%. The latter is a simple and reliable method for diagnosing systemic amyloidosis.
Differential Diagnosis
When evaluating a patient with suspected primary amyloidosis, it is important to consider other causes of the presenting symptoms and signs, including multiple myeloma, hemochromatosis, sarcoidosis, Waldenström's macroglobulinemia, metastatic tumors, and other cause of nephrotic syndrome, such as lupus nephritis.
Treatment
Treatment of localized amyloid tumors is by surgical excision. There is no effective treatment of systemic amyloidosis, and death usually occurs within 1–3 years. Care is generally supportive, although hemodialysis and immunosuppressive therapy may be useful. When concomitant multiple myeloma is found, it is treated in the standard way (see Hematology). Secondary disease is usually approached by aggressively treating the predisposing disease, but remission of fibril deposition does not occur. Bone marrow transplant after chemotherapy has been used in selected patients.
Heavy Chain Disease (, , )
These are rare disorders in which the abnormal serum and urine protein is a part of a homogeneous ,
, or
heavy chain. The clinical presentation is more typical of lymphoma than multiple myeloma, and there are no destructive bone lesions.
chain disease presents as a lymphoproliferative disorder with autoimmune features.
chain disease is frequently associated with severe diarrhea and infiltration of the lamina propria of the small intestine with abnormal plasma cells.
chain disease is associated with chronic lymphocytic leukemia.

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Vesole DH et al; Plasma Cell Disorders Working Committee of the Center for International Blood and Marrow Transplant Research. High-dose therapy and autologous hematopoietic stem cell transplantation for patients with primary systemic amyloidosis: a Center for International Blood and Marrow Transplant Research Study. Mayo Clin Proc. 2006 Jul;81(7):880–8. [PMID: 16835967]