Amylodosis Resource - Uptodate SUMMARY AND RECOMMENDATIONS ●Types of amyloidosis – Amyloidosis is a generic term for the extracellular tissue deposition of fibrils composed of low molecular weight subunits of a variety of proteins, Major forms of amyloidosis include: •AL amyloidosis / Primary Amyloidosis– Due to deposition of protein derived from immunoglobulin light chain fragments. It is a potential complication of any plasma cell dyscrasia that produces monoclonal immunoglobulin. •Transthyretin amyloidosis (ATTR) / familial Amyloidosis - Due to either specific Note : Initial ix - monoclonal protein testing Note : FLC assays are more sensitive for the detection of monoclonal FLCs than urine immunofixation. The presence of a monoclonal protein alone is not sufficient to make a diagnosis of AL amyloid unless light chains have been demonstrated within the amyloid deposits. Heritable types of amyloidosis should be excluded if a plasma cell dyscrasia cannot be documented. ●Treatment – Treatment of amyloidosis generally varies with the cause of fibril production. As examples, treatment is aimed at the underlying infectious or inflammatory disorder in AA amyloidosis, at the underlying plasma cell dyscrasia in AL amyloidosis, and at either altering the mode of dialysis or considering renal transplantation in patients with dialysis-related amyloidosis. Liver transplantation may be effective in certain of the hereditary amyloidoses. Therapies to decrease TTR production are available, and treatments that promote the clearance of amyloid deposits of different types are in development. heritable mutations, which are associated with familial amyloid polyneuropathy (FAP) and/or familial amyloid cardiomyopathy, or which more often may occur in a nonfamilial form as a concomitant of aging without apparent mutations (wild-type transthyretin [TTR] amyloidosis •AA amyloidosis/ Secondary Amyloidosis – The most common form in resourcelimited countries, it may complicate chronic diseases associated with ongoing or recurring inflammation, such as chronic infections; rheumatoid arthritis (RA), spondyloarthritis, or inflammatory bowel disease; or periodic fever syndromes. Additional major forms include dialysis-related amyloidosis, other heritable amyloidoses, other age-related amyloidoses, organ-specific amyloid, and others ●Clinical manifestations – Clinical manifestations vary depending upon the type of amyloid and the distribution of deposition. Some features that suggest amyloidosis include waxy skin and easy bruising, enlarged muscles (eg, tongue, deltoids), heart failure, cardiac conduction abnormalities, hepatomegaly, heavy proteinuria or the nephrotic syndrome, peripheral and/or autonomic neuropathy, and impaired coagulation. ●Diagnosis – Tissue biopsy should be used to confirm the diagnosis in all cases. Fat pad aspiration biopsy is less likely than liver, renal, or rectal biopsy to be complicated by serious bleeding; we thus suggest it as the initial biopsy technique for patients with other than singleorgan involvement. In patients with single-organ involvement, biopsy of the clinically involved site is suggested because fat pad aspiration biopsy has a low sensitivity for amyloidosis in such patients. ●Monoclonal protein testing – Patients with biopsy-documented amyloidosis and a well- defined plasma cell dyscrasia (eg, multiple myeloma or Waldenström macroglobulinemia) need not undergo further testing for an underlying hematologic disorder. Patients without a known plasma cell disorder should be tested to determine whether a monoclonal protein is present in serum, urine, or both using a combination of serum and urine protein electrophoresis, followed by immunofixation. Quantitation of serum free light chains (FLCs) is suggested for AL patients who do not have monoclonal proteins by immunofixation. Diagnostic approaches — The definitive method for diagnosis of amyloidosis is tissue biopsy, although the presence of amyloidosis may be suggested by the history and clinical manifestations (eg, nephrotic syndrome in a patient with multiple myeloma or longstanding, active RA) (see 'When to suspect amyloidosis' above). In many patients, the biopsy need not be from the known affected organ but can be from another site likely to have deposits, most often the bone marrow or abdominal fat pad (see 'Selection of biopsy site' below). In some patients, the presence of amyloid is demonstrated by findings on imaging (see 'Imaging' below). In some patients, a biopsy result consistent with amyloid is an unexpected diagnosis following routine laboratory Congo Red staining. As an example, AA amyloidosis is only one cause of the nephrotic syndrome in patients with RA; other causes include drug side effects, immune-complex disease, or an unrelated disorder.