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.