QUIZ OF THE WEEK By .. Shada AlGhamdi

Amyloidosis

INTRODUCTION..  Amyloidosis is a general term refer to the extracellular tissue deposition of fibrils composed of low molecular weight subunits of a variety of proteins.

Amyloidosis types.. AL amyloidosis: due to deposition of protein derived from immunoglobulin light chain fragments. protein is detectable in urine and/or serum symptoms and signs: heavy proteinuria (usually in the nephrotic range) edema hepatosplenomegaly unexplained heart failure carpal tunnel syndrome

may complicate chronic diseases such as .. rheumatoid arthritis (RA) AA amyloidosis: may complicate chronic diseases such as .. rheumatoid arthritis (RA) spondyloarthropathy inflammatory bowel disease chronic infections The most common organ system involved in AA amyloid is the kidney (about 80 percent). This is usually characterized by glomerular amyloid deposition, typically leading to the nephrotic syndrome, Cardiac and other organ involvement may also be seen.

Dialysis-related amyloidosis: Due to deposition of fibrils derived from beta-2 microglobulin, which accumulate in patients with end-stage renal disease who are being maintained for prolonged periods of time by dialysis.

Age-related (senile) systemic amyloidosis:  Deposition of otherwise normal (wild-type) transthyretin in myocardium and other sites may result in a form of amyloidosis that is referred to as systemic senile amyloidosis (SSA)

Organ-specific amyloid:  Amyloid deposition can be isolated to a single organ, such as skin eye heart pancreas genitourinary tract Examples: Alzheimer disease in which plaques and amyloid-laden cerebral vessels are composed of the beta protein (Ab).

CLINICAL MANIFESTATIONS amount of amyloid deposition type of precursor protein tissue distribution

DIAGNOSIS.. confirmed only by tissue biopsy history and clinical manifestations findings on imaging.

Biopsies.. can be obtained from either clinically uninvolved sites, such as subcutaneous fat, minor salivary glands, or rectal mucosa; or from dysfunctional organs (eg, kidney, nerve). Aspiration or biopsy of subcutaneous fat with Congo red staining and examination using polarizing microscopy has an overall sensitivity of 57 to 85 percent and a specificity of 92 to 100 percent for primary (AL) or secondary (AA) amyloidosis The diagnostic sensitivity is higher in those with multiorgan involvement who are suspected of having systemic amyloidosis Fat pad aspiration or biopsy has a low sensitivity for amyloidosis in patients with a single involved organ.

Histopathology and protein analysis..  The amyloid deposits appear as amorphous hyaline material on light microscopy. The fibrils bind Congo red (leading to green birefringence under polarized light) and thioflavine T (producing an intense yellow-green fluorescence).

Imaging scanning.. Examples: speckled appearance of the myocardium on echocardiography, avid uptake over the heart by 99-Technetium scintigraphy in ATTR amyloidosis, delayed subendothelial gadolinium enhancement on cardiac magnetic resonance imaging (MRI), lytic bone lesions in multiple myeloma cystic bone lesions in dialysis-related amyloidosis. Imaging scanning.. 

TREATMENT.. Treatment of the different types of amyloidosis varies with the cause of fibril production. Secondry AA amyloidosis: Therapy is aimed at the underlying infectious or inflammatory disorder (AL) amyloidosis: treating the underlying plasma cell dyscrasia in primary Dialysis-related amyloidosis: either altering the mode of dialysis or considering renal transplantation Hereditary amyloidoses in which the mutant amyloid precursor protein is produced by the liver (eg, transthyretin, apolipoprotein A-I, and fibrinogen Aa), liver transplantation may in some instances prevent further deposition of amyloid and may lead to regression of established deposits. Transplantation during the first year after appearance of symptoms is ideal. Patients with sporadic or undiagnosed hereditary amyloidosis who present with advanced end-organ damage may benefit from combined hepatorenal or hepatocardiac transplantation.

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