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Amyloidosis |
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Amyloidosis results from the deposition of insoluble, fibrous amyloid proteins, nearly always in the extracellular spaces of organs and tissues. The most common form of systemic amyloidosis seen in current clinical practice is AL (primary idiopathic amyloidosis, or that associated with multiple myeloma) resulting from fibril formation by monoclonal antibody light chains in primary amyloidosis and in some cases of multiple myeloma. Less than 20 percent of patients with AL have myeloma. The rest have other monoclonal gammopathies, light chain disease, or even agammablobulinemia (producing light chains, but not intact immunoglobulin).
AA amyloidosis (secondary, reactive, or acquired amyloidosis) occurs most frequently as a complication of chronic inflammatory disease. Effective treatment of the underlying inflammatory condition has reduced incidence in developed countries. In the past in the United States, tuberculosis, osteomyelitis, and leprosy.
Until the advent of biochemical studies, there was no generally accepted nosology for the heredofamilial amyloid syndromes. Some researchers emphasized the site of predominant organ involvement, classifying the disease as neuropathic, nephropathic, or cardiopathic amyloidosis, while others stressed the genetic aspects. With one exception, the amyloidosis of FMF, which is inherited as an autosomal recessive disorder and is an AA type of, amaloidosis, ameloidosis.
Depending upon the biochemical nature of the amyloid fibril protein, instead of systemic deposition involving the cardiovascular and gastrointestinal systems along with lymph nodes, spleen, liver, kidneys, and adrenals, amyloid deposition may be limited to a single organ such as the pancreas, brain.
The clinical manifestations of amyloidosis are varied and depend entirely on the biochemical nature of the fibril protein and thus the area of the body that is involved. The diagnosis of amyloidosis is usually not made until after the point of irreversible organ damage. Proteinuria is often the first symptom associated with systemic amyloidosis.
Kidney
Renal involvement may consist of mild proteinuria or frank nephrosis. In some cases, the urinary sediment may show a few red blood cells. The renal lesion is usually not reversible and in time leads to progressive azotemia and death. The prognosis does not appear to be related to the degree of the proteinuria.
With respect to systemic amyloidoses, cardiac amyloidosis is common in primary (AL) and heredofamilial amyloidosis and very rare in the secondary (AA) form. With respect to localized amyloidosis, cardiac amyloidosis of the TTR type is common after 80 years of age; also atrial natriuretic factor may be present in the atria.
While hepatic involvement is common except in heredofamilial amyloidosis of the TTR type, liver function abnormalities are minimal and occur late in the disease. Portal hypertension occurs but is uncommon. Intrahepatic cholestasis has been noted in about 5 percent of patients with AL (primary) amyloidosis. Hepatomegaly is common, and AL hepatic amyloid.
Involvement of the skin is one of the most characteristic manifestations of primary (AL) amyloidosis.
Gastrointestinal symptoms are common in all systemic types of amyloidosis. They may result from direct involvement of the gastrointestinal tract at any level or from infiltration of the autonomic nervous system with amyloid. The symptoms include those of obstruction, ulceration, malabsorption, hemorrhage, protein loss.
Neurologic manifestations may include peripheral neuropathy, postural hypotension, inability to sweat, Adies's pupil, hoarseness, and sphincter incompetence. These manifestations are especially prominent.
Amyloid may infiltrate the thyroid or other endocrine glands but rarely causes endocrine dysfunction. Local amyloid deposits almost invariably accompany medullary carcinoma of the thyroid.