Macular Amyloidosis

Updated: Oct 26, 2017
  • Author: Sultan Al-Khenaizan, MBBS, FRCPC; Chief Editor: William D James, MD  more...
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Overview

Practice Essentials

Primary localized cutaneous amyloidosis (PLCA) is characterized by extracellular deposition of heterogeneic amyloid proteins in the skin without systemic involvement. Types of PLCA include the following:

  • Macular amyloidosis
  • Lichen amyloidosis
  • Nodular amyloidosis

Macular amyloidosis is thought to result from a combination of genetic and environmental causes with prolonged friction a key pathogenic factor. However, the precise molecular mechanisms underlying its pathogenesis are not known. [1] Macular amyloidosis has been reported in association with multiple endocrine neoplasia type 2A. The cardinal triad of this autosomal dominant syndrome is medullary thyroid carcinomapheochromocytoma, and hyperparathyroidism. [2]

Macular amyloidoisis is a chronic disease. Cosmetic disfigurement and severe pruritus  significantly impair quality of life. In a study of 101 Chinese patients with PLCA, Fang et al reported significantly decreasing average scores in social functioning and mental health due to pruritus. Because of its significant impact on quality of life, pruritus management is an important component of treatment. Additionally, the study found that lesions on visible parts of the body, such as the face and hands, decrease quality of life more than lesions that can be hidden. [3]

Macular amyloidoisis is usually diagnosed clinically. The most common dermoscopic finding of macular amyloidosis is a central hub of either white or brown surrounded by various configurations of brownish pigmentation, including fine radiating streaks, dots, leaf-like projections, and bulbous projections. [4]   For cases with atypical presentations, skin biopsy may be necessary.

Therapeutic modalities that have been suggested include topical and systemic medications, phototherapy, electrodessication, dermabrasion, cryosurgery, and lasers. However, evidence from randomized, controlled trials is lacking, and effectiveness is based on small studies and case reports. No standardized treatment has been established. [5]   

The incidence of macular amyloidosis is more common among Asians, Middle Easterners, and South Americans than in other people. In many studies, macular amyloidosis seems to affect women more frequently than men. Macular amyloidosis is a disease of the adult population.

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Background

 

 

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Pathophysiology

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 and of indefinite length and arranged in a loose meshwork. [6]

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. [7]

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

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. [8] 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) and has been identified in both Brazilian and Chinese families with manifestations of familial primary localized cutaneous amyloidosis. [9, 10, 11]

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: fibrillar body theory and secretory theory. These theories are not mutually exclusive, and both could be possible.

Fibrillar body theory

Fibrillar body theory was proposed by Hashimoto and 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. [12, 13] 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

Secretory 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. [14]

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