Show Summary Details
Page of

Amyloidosis 

Amyloidosis

Chapter:
Amyloidosis
Author(s):

M.B. Pepys

and P.N. Hawkins

DOI:
10.1093/med/9780199204854.003.121203_update_001

February 27, 2014: This chapter has been re-evaluated and remains up-to-date. No changes have been necessary.

Update:

Key aspects of AL, AA, ATTR, Aβ‎2m and ALECT2 amyloidosis, including both molecular mechanisms and treatment. Update on cerebral amyloid angiopathy (CAA).

Updated on 28 Nov 2013. The previous version of this content can be found here.
Page of

PRINTED FROM OXFORD MEDICINE ONLINE (www.oxfordmedicine.com). © Oxford University Press, 2015. All Rights Reserved. Under the terms of the licence agreement, an individual user may print out a PDF of a single chapter of a title in Oxford Medicine Online for personal use (for details see Privacy Policy).

date: 30 March 2017

Amyloidosis is the clinical condition caused by extracellular deposition of amyloid in the tissues. Amyloid deposits are composed of amyloid fibrils, abnormal insoluble protein fibres formed by misfolding of their normally soluble precursors. About 30 different proteins can form clinically or pathologically significant amyloid fibrils in vivo as a result of either acquired or hereditary abnormalities. Small, focal, clinically silent amyloid deposits in the brain, heart, seminal vesicles, and joints are a universal accompaniment of ageing. However, clinically important amyloid deposits usually accumulate progressively, disrupting the structure and function of affected tissues and lead inexorably to organ failure and death. No treatment yet exists which can specifically clear amyloid deposits, but intervention which reduces the availability of the amyloid fibril precursor proteins may lead to amyloid regression with clinical benefit.

Pathology—amyloid fibrils of all types are similar: straight, rigid, and non branching; of indeterminate length and 10–15 nm in diameter; and with their subunit proteins arranged in a stack of twisted antiparallel β‎-pleated sheets. The fibrils bind Congo red dye producing pathognomonic green birefringence when viewed in polarized light, and the protein type can be identified by immunostaining or proteomic analysis. Amyloid deposits always contain a non fibrillar plasma glycoprotein, amyloid P component, the universal presence of which is the basis for use of radioisotope-labelled serum amyloid P component as a diagnostic tracer.

Clinicopathological correlation—amyloid may be deposited in any tissue of the body, including blood vessels walls and connective tissue matrix; clinical manifestations are correspondingly diverse. Although there are some typical clinical presentations related to fibril type, there are many forms of amyloidosis in which there is little or no concordance between the fibril protein, or the genotype of its precursor, and the clinical phenotype. Identification of the amyloid fibril protein is always essential for appropriate clinical management.

Specific types of amyloidosis

Reactive systemic (AA) amyloidosis—fibrils composed of AA protein derived from the acute phase protein, serum amyloid A protein (SAA). Occurs as a complication of any chronic inflammatory disorders (e.g. rheumatoid arthritis) or infections in which SAA concentrations are persistently increased. Most commonly presents with proteinuria and/or organomegaly, e.g. hepatosplenomegaly; nephrotic syndrome may develop before progression to endstage renal failure. Treatment is directed towards the underlying condition, aiming to reduce SAA values to normal.

Monoclonal immunoglobulin light chain (AL) amyloidosis—fibrils consists of all or part of the variable (VL) domain of monoclonal immunoglobulin light chains. May complicate any B-cell dyscrasia but most cases are associated with otherwise ‘benign’ monoclonal gammopathy. Highly variable idiotypic disease but characteristic presentations include involvement of the heart (restrictive cardiomyopathy), kidneys (proteinuria, renal failure), gut (motility disorders, malabsorption), tongue (macroglossia), and nerves (painful sensory polyneuropathy). Treatment is cytotoxic chemotherapy aimed at suppression of the causative B–cell clone, similar to that used in myeloma.

Hereditary systemic amyloidoses—include familial amyloid polyneuropathy, which is caused by mutations in the gene for the plasma protein transthyretin and characterized by progressive peripheral and autonomic neuropathy and varying degrees of visceral involvement.

Access to the complete content on Oxford Medicine Online requires a subscription or purchase. Public users are able to search the site and view the abstracts for each book and chapter without a subscription.

Please subscribe or login to access full text content.

If you have purchased a print title that contains an access token, please see the token for information about how to register your code.

For questions on access or troubleshooting, please check our FAQs, and if you can''t find the answer there, please contact us.