Amyloidosis
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Contents |
More Specific Terms
- AA amyloidosis
- AL amyloidosis
- amyloidosis type 8 (AMYL8); systemic non-neuropathic amyloidosis; Ostertag-type amyloidosis
- cardiac amyloidosis
- cerebral amyloid angiopathy
- familial amyloid polyneuropathy
- familial amyloidosis
- familial Mediterranean fever (FMF, recurrent polyserositis)
- Finnish type amyloidosis; amyloidosis type 5; Meretoja type amyloidosis
- hemodialysis-related amyloidosis
- lattice dystrophy
- localized cutaneous amyloidosis
- oculoleptomeningeal type amyloidosis (amyloidosis VII)
- primary localized cutaneous amyloidosis; familial lichen amyloidosis
- renal amyloidosis
- senile systemic amyloidosis
Introduction
Etiology
- primary ( idiopathic)
-
- intracellular accumulation of beta amyloid?
- secondary
- chronic suppuration or tissue breakdown ( AA amyloidosis)
- long-term dialysis ( beta-2 microglobulin)
- amyloid light-chain ( AL) amyloidosis (most common)
- overproduction of monoclonal light chains (80% lambda)
- a localized amyloidosis involving a single organ with deposition of light chains may occur
- Protein precursors of amyloidosis/amyloid deposits:
- serum amyloid ( SAA)
- apolipoprotein A-I (ApoAI)
- apolipoprotein A-II (ApoAII)
- immunoglogulin light & heavy chains
- beta-2-microglobulin
- procalcitonin
- islet amyloid peptide/ amylin
- atrial natriuretic peptide
- prolactin
- gelsolin
- keratin (cutaneous amyloid)
- keratoepithelin
- transthyretin
- amyloid precursor protein
- prion protein
- BRI gene product
- cystatin-C
- fibrinogen alpha chain
- medin/ lactadherin
- lysozyme
Pathology
- serum amyloid P component ( SAP) binds to all forms of amyloid fibrils & is present in all amyloid desposits including amyloid of Alzheimer's disease
- senile systemic amyloidosis most frequently involves the heart
- prealbumin is characteristic protein in familial amyloidosis
- cardiac abnormalities are not a feature of secondary amyloidosis
- increased risk of hemorrhage
- systemic fibrinolysis
- acquired factor X deficiency
- absorption of factor X to amyloid fibrils
- increased vascular fragility
Genetics
- autosomal dominant (familial form)
Clinical-manifestations
- depend on organ (systems) involved
- asthenia
- weight loss
- paresthesias
- macroglossia
- hypertension
- lymphadenopathy
- hepatomegaly
- splenomegaly
- petechiae, purpura
- nephrotic syndrome
- edema
- arthralgia
- myalgia
- joint effusion
- cardiomyopathy ( AL or monoclonal Ig-associated)
Laboratory
- biopsy of gingiva
- biopsy of rectum
- aspiration of abdominal fat pad
- yellow-green birefringence in polarized light
- work up for multiple myeloma if indicated
- PT & aPTT may be increased due to factor X deficiency
- fibrinogen may be diminished
- serum beta-2 microglobulin
- increased alkaline phosphatase is the 1st indication of liver involvement
- negative findings:
- serum complement levels are normal
- antinuclear antibody ( ANA) is negative
- rheumatoid factor ( RF) is negative
Management
- treatment of underlying disease
- AL amyloidosis is treated with chemotherapy (see multiple myeloma)
- AA amyloid is treated by aggressively treating the inflammatory condition that generates the increased SAA levels
- NO effective treatment for beta-2 microglobulin-related amyloidosis
- a novel investigational approach is described [6] in which a small molecule binds serum amyloid followed with monoclonal antibody directed at amyloid deposits, stimulating macrophages to engulf the amyloid deposits
More General Terms
Additional Terms
References
- Stedman's Medical Dictionary 27th ed, Williams & Wilkins, Baltimore, 1999
- Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 54-55
- Medical Knowledge Self Assessment Program (MKSAP) 11, 14, American College of Physicians, Philadelphia 1998, 2006
- Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1307
- Merlini G & Bellotti V, Molecular Mechanisms of amylodosis. N Engl J Med 349:583, 2003 PMID: &dopt=Abstract
- van der Hilst JC et al, Molecular Mechanisms of amylodosis. N Engl J Med 349:1872, 2003 PMID: [1]
- Sungar CI, Molecular Mechanisms of amylodosis. N Engl J Med 349:1872, 2003 PMID: [2] - Bodin K et al. Antibodies to human serum amyloid P component eliminate visceral amyloid deposits. Nature 2010 Nov 4; 468:93. PMID: [3]
