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AT-A-GLANCE

AT-A-GLANCE

  • There are 36 types of amyloid disease, defined by the subunit proteins that constitute the fibrils in these disorders, 11 of which involve the skin.

  • Cutaneous amyloidosis may reflect a systemic form of amyloid, or be localized to the skin and/or mucous membranes.

  • Precursors of fibril subunit proteins may circulate in blood and/or be synthesized locally; they may be wildtype or mutant molecules that can be typed by DNA sequencing.

  • Amyloid in skin may be sampled by lesional biopsy or abdominal fat pad aspiration or biopsy; it is characterized by metachromasia and apple-green birefringence after staining with Congo red, or yellow-green fluorescence after staining with thioflavin T.

  • Deposits may localize to the papillary dermis (macular and lichen amyloidosis) or be characterized by congophilic angiopathy and involvement of adnexal structures (nodular amyloidosis).

  • Amyloid can be typed by immunohistochemistry, immunoelectron microscopy, and/or laser capture mass spectroscopy followed by protein sequencing.

  • Treatment of amyloid diseases is determined by the fibril subunit protein, associated clinical manifestations, and whether disease is systemic or localized.

  • Treatment strategies include suppression of precursor protein, disruption of oligomers and/or fibrils, and/or enhanced clearance of deposits.

  • Localized cutaneous amyloidoses present specific challenges and opportunities for diagnosis and therapy because of the accessibility of skin lesions, association in some cases with defined genetic abnormalities, and multifactorial etiologies for itch in pathogenesis.

DEFINITION

Amyloid is a pathologic entity characterized by the presence of mostly extracellular homogenous hyaline material that is typically metachromatic, as seen by color changes of dyes such as Congo red (actually orange in solution), crystal violet (which yields a deep red-purple color on a blue background), or sodium sulfate Alcian blue (reacts with proteoglycan in amyloid deposits to yield a green color). Other stains that can be used include cotton dyes such as Sirius red (a polyazo dye) and Pagoda red. Amyloid is further defined in tissue section as yielding apple-green birefringence by polarizing microscopy after staining with Congo red, and as having typical yellow-green fluorescence after staining with thioflavin T. Ultrastructurally, the main constituents of deposits are fibrils which are 10 to 15 nm in diameter, and variable in length, that accumulate in the extracellular space, and can be visualized by electron microscopy.

A second feature of all amyloid deposits is the presence of a pentraxin, serum amyloid P-component (SAP). In addition to the fibril and SAP, deposits are enriched in heparan sulfate proteoglycan, as well as a number of proteins that have been identified by extraction of amyloid from tissue. These other substances include several apolipoproteins, notably apoE, apoJ, and apoA4.1 Thus the diagnosis of amyloidosis is rigorously defined by the appearance, tinctorial properties and ultrastructural features of biopsied material (Table 125-1).

Table 125-1Histologic Criteria for the Definition of Amyloid

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