Macular Amyloidosis

Updated: Dec 11, 2015
  • Author: Sultan Al-Khenaizan, MBBS, FRCPC; Chief Editor: William D James, MD  more...
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Overview

Background

Amyloidosis is a generic term that signifies the abnormal extracellular tissue deposition of one of a family of biochemically unrelated proteins that share certain characteristic staining properties, including apple-green birefringence of Congo red–stained preparations viewed under polarizing light. Under electron microscopy (EM), amyloid deposits are composed of linear, nonbranching, aggregated fibrils that are 7.5-10 nm thick of indefinite length arranged in a loose meshwork. [1]

X-ray diffraction crystallography and infrared spectroscopy reveal that these fibrils have a meridional, antiparallel, beta-pleated sheet configuration, with polypeptide chains arranged perpendicular to the long axis of the fibrils.

Amyloid deposits contain (in addition to the fibrillar component) a nonfibrillar protein referred to as amyloid-P (Am-P). This protein is identical to normal plasma globulin, known as serum amyloid-P (SAP). Am-P constitutes 14% of the dry weight of amyloid. This protein is also found in the microfibrillar sheath of elastic fibers. SAP is closely related to the acute phase reactant C-reactive protein (CRP) and has been shown to be an elastase inhibitor. [2]

The SAP and the beta-pleated sheet configurations are thought to protect amyloid deposits from degradation and phagocytosis, leading to persistence of the deposits.

Macular amyloidosis has been reported in association with Sipple syndrome. The cardinal triad of this autosomal dominant syndrome is medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism.

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Pathophysiology

Amyloid deposits in macular amyloidosis and lichen amyloidosis bind to antikeratin antibodies. These deposits contain sulfhydryl groups pointing to altered keratin as a source for these deposits. Apaydin et al found no differences in staining characteristics of cytokeratins between macular amyloidosis and lichen amyloidosis. [3] Interestingly, in their study, all the cytokeratins detected in amyloid deposits were of basic type (type II). This may be because, in amyloidogenesis, acidic cytokeratins such as cytokeratin 14 are degraded faster than basic types.

A pathogenic missense mutation was identified in the OSMR gene that encodes the oncostatin M (OSM) receptor β (OSMR-β) in a Brazilian pedigree. [4, 5]

The exact origin of amyloid deposits in macular amyloidosis has not been determined. Two theories have been proposed to explain the origin of the amyloid deposits. These theories are not mutually exclusive, and both could be possible.

Fibrillar body theory

This theory proposed by Hashimoto suggests that the necrotic epidermal cells (colloid bodies) are transformed into amyloid by dermal macrophages and fibroblasts by a process called filamentous degeneration. The absence of amyloid deposits in other dermatoses with colloid bodies (eg, lichen planus) is explained by the brisk inflammatory reaction clearing them promptly in lichen planus, while the lack of inflammatory cells leads to the formation of amyloid deposits in macular amyloidosis. [6, 7] This theory does not explain how the alpha type of keratin tertiary structure is degraded and converted into the beta-pleated sheet configuration of amyloid.

Secretory theory

This theory proposed by Yamagihara et al suggests that the amyloid in macular amyloidosis is secreted by disrupted basal cells and is assembled at the dermoepidermal junction. [8]

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Epidemiology

Race

The incidence of macular amyloidosis is more common among Asians, Middle Easterners, and South Americans than in other people.

Sex

In many studies, macular amyloidosis seems to affect women more frequently than men.

Age

Macular amyloidosis is a disease of the adult population.

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