Amyloidosis



Amyloidosis


Patricia Woo



Amyloidosis is characterized by the deposition of a homogenous eosinophilic material in the parenchyma and around blood vessels. Amyloidosis was originally divided into two types: primary amyloidosis in association with plasma cell disorders, which occurs as an idiopathic or familial disease, and secondary amyloidosis, found in conjunction with another inflammatory disease (e.g., juvenile rheumatoid arthritis, familial Mediterranean fever [FMF], chronic pulmonary disease, or osteomyelitis). A classification of different types of amyloidoses is summarized in Table 435.1.

In primary or amyloid-containing immunoglobulin light-chain amyloidosis (see Table 435.1), the principal sites of involvement are the skin and gastrointestinal tract. The patient may present with macroglossia, carpal tunnel syndrome or arthritis, congestive heart failure, malabsorption, or gastrointestinal bleeding. In secondary or amyloid A (AA) amyloidosis (see Table 435.1), the patient develops hepatomegaly, splenomegaly, and nephrotic syndrome. Secondary amyloidosis is a rare occurrence in children, but it is seen in association with Hodgkin disease or renal carcinoma, in addition to the inflammatory diseases mentioned previously. In young adults, it increases in frequency in chronic suppurative conditions, with the infectious complications of intravenous drug use, and in diseases such as leprosy or malaria. Amyloidosis has also been described in endocrine organs, in association with diabetes and thyroid disease and as localized cutaneous deposits (see Table 435.1).


PATHOLOGY

All amyloid deposits display a green birefringence when stained with Congo red dye and viewed under a polarizing microscope. These deposits appear microscopically homogenous. The major component of amyloid deposits by electron microscopy is a 100-Å fibril that is thin, nonbranching, and rigid. Although the ultrastructural appearances of the fibrils in the various types of amyloidoses are nearly identical, their biochemical compositions are distinct. These fibrils assume a predominantly antiparallel beta-pleated sheet conformation by x-ray crystallography. In primary or AL amyloidosis, the amino acid sequence is homologous with the variable region of immunoglobulin light chains.

In secondary or AA amyloidosis, the major fibrillar protein is not immunoglobulin light chains. A serum component that circulates normally in very low concentrations, serum amyloid A (SAA), is the precursor protein for these amyloid fibrils. SAA is an acute-phase protein, and a chronic elevation of SAA is part of the prerequisite for the pathogenesis of AA amyloidosis. A serum P component exists that is an alpha1-glycoprotein that is adsorbed onto the fibrillar structure. This pentagonal component is common to all types of amyloids, but it constitutes only approximately 5% of the deposits. The serum amyloid P (SAP) component is a doughnut-shaped structure composed of five identical subunits closely related in structure and function to C-reactive protein. The remainder of the fibrils are composed of glycosaminoglycans and small amounts of matrix proteins.


Hereditary Amyloidosis

The most common type of hereditary amyloidosis is that associated with FMF, a periodic disease inherited as an autosomal recessive trait. FMF is particularly common in Jews, Turks, Armenians, and Levantine Arabs. The onset of disease occurs generally in individuals between the ages of 5 and 15 years. Each stereotypic exacerbation is characterized by fever, abdominal and pleuropericardial pain, and arthritis. An attack begins acutely and may last for 1 week before slowly subsiding. The gene (pyrin) for FMF has been described and is located on chromosome 16; patients with FMF have mutations of this gene. FMF-associated amyloidosis occurs in certain ethnic groups only (e.g., North African Jews), affecting children and resulting
in the nephrotic syndrome and eventual death from renal failure. FMF and amyloidosis may be inherited separately.

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Jul 24, 2016 | Posted by in ORTHOPEDIC | Comments Off on Amyloidosis
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