Introduction
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.
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.
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 (MA) has been reported in association with Sipple syndrome. The cardinal triad of this autosomal dominant syndrome is medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism.
Pathophysiology
Amyloid deposits in MA and lichen amyloidosis (LA) 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 MA and LA. 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.
The exact origin of amyloid deposits in MA 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 MA. 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 MA is secreted by disrupted basal cells and is assembled at the dermoepidermal junction (DEJ).
Race
The incidence of MA is more common among Asians, Middle Easterners, and South Americans than in other people.
Sex
In many studies, MA seems to affect women more frequently than men.
Age
MA is a disease of the adult population.
Clinical
History
MA is a pruritic eruption that is variable in severity. Frequently, patients seek medical attention because of the hyperpigmentation.
Physical
MA is a pruritic eruption consisting of small, dusky-brown or grayish pigmented macules distributed symmetrically over the upper back and, in some patients, the arms.
Although a reticulated or rippled pattern of pigmentation has been emphasized as a characteristic and diagnostic feature of MA, in 2 case series, less than 50% of patients had this feature.
Causes
Constant friction and rubbing with a nylon brush or towel may cause MA.
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References
Apaydin R, Gürbüz Y, Bayramgürler D, et al. Cytokeratin expression in lichen amyloidosus and macular amyloidosis. J Eur Acad Dermatol Venereol. May 2004;18(3):305-9. [Medline].
Black MM, Jones EW. Macular amyloidosis. A study of 21 cases with special reference to the role of the epidermis in its histogenesis. Br J Dermatol. Mar 1971;84(3):199-209. [Medline].
Breathnach SM, Bhogal B, Dyck RF, et al. Immunohistochemical demonstration of amyloid P component in skin of normal subjects and patients with cutaneous amyloidosis. Br J Dermatol. Aug 1981;105(2):115-24. [Medline].
Breathnach SM, Melrose SM, Bhogal B, et al. Amyloid P component is located on elastic fibre microfibrils in normal human tissue. Nature. Oct 22 1981;293(5834):652-4. [Medline].
Breathnach SM. Amyloid and amyloidosis. J Am Acad Dermatol. Jan 1988;18(1 Pt 1):1-16. [Medline].
Brownstein MH, Hashimoto K, Greenwald G. Biphasic amyloidosis: link between macular and lichenoid forms. Arch Dermatol. Sep 1972;106(3):419. [Medline].
Cortes A. Primary cutaneous amyloidosis. Dermatologica. 1969;139(2):109-14. [Medline].
Eanes ED, Glenner GG. X-ray diffraction studies on amyloid filaments. J Histochem Cytochem. Nov 1968;16(11):673-7. [Medline].
Eriksson S, Janciauskiene S, Merlini G. The putative role of alpha-1-antitrypsin in the disaggregation of amyloid lambda fibrils. J Intern Med. Feb 1995;237(2):143-9. [Medline].
Glenner GG. Amyloid deposits and amyloidosis. The beta-fibrilloses (first of two parts). N Engl J Med. Jun 5 1980;302(23):1283-92. [Medline].
Hashimoto K, Kobayashi H. Histogenesis of amyloid in the skin. Am J Dermatopathol. Summer 1980;2(2):165-71. [Medline].
Hashimoto K, Ito K, Kumakiri M, Headington J. Nylon brush macular amyloidosis. Arch Dermatol. May 1987;123(5):633-7. [Medline].
Horiguchi Y, Fine JD, Leigh IM, et al. Lamina densa malformation involved in histogenesis of primary localized cutaneous amyloidosis. J Invest Dermatol. Jul 1992;99(1):12-8. [Medline].
Hsieh SD, Yamamoto R, Saito K, et al. Amyloidosis presented with whitening and loss of hair which improved after dimethylsulfoxide (DMSO) treatment. Jpn J Med. Aug 1987;26(3):393-5. [Medline].
Hudson LD. Macular amyloidosis: treatment with ultraviolet B. Cutis. Jul 1986;38(1):61-2. [Medline].
Kibbi AG, Rubeiz NG, Zaynoun ST, Kurban AK. Primary localized cutaneous amyloidosis. Int J Dermatol. Feb 1992;31(2):95-8. [Medline].
Kobayashi H, Hashimoto K. Amyloidogenesis in organ-limited cutaneous amyloidosis: an antigenic identity between epidermal keratin and skin amyloid. J Invest Dermatol. Jan 1983;80(1):66-72. [Medline].
Kurban AK, Malak JA, Afifi AK, Mire J. Primary localized macular cutaneous amyloidosis: histochemistry andelectron microscopy. Br J Dermatol. Jul 1971;85(1):52-60. [Medline].
Lambert WC. Cutaneous deposition disorders. In: Farmer ER, Hood AF, eds. Pathology of the Skin. Norwalk, Conn: Appleton & Lange; 1990:. 432-50.
Li JJ, McAdam KP. Human amyloid P component: an elastase inhibitor. Scand J Immunol. Sep 1984;20(3):219-26. [Medline].
Lim KB, Tan SH, Tan KT. Lack of effect of dimethyl sulphoxide (DMSO) on amyloid deposits in lichenamyloidosis. Br J Dermatol. Sep 1988;119(3):409-10. [Medline].
Monfrecola G, Iandoli R, Bruno G, Martellotta D. Lichen amyloidosus: a new therapeutic approach. Acta Derm Venereol. 1985;65(5):453-5. [Medline].
Ozkaya-Bayazit E, Kavak A, Gungor H, Ozarmagan G. Intermittent use of topical dimethyl sulfoxide in macular and papularamyloidosis. Int J Dermatol. Dec 1998;37(12):949-54. [Medline].
Piette WW. Myeloma, paraproteinemias, and the skin. Med Clin North Am. Jan 1986;70(1):155-76. [Medline].
Ruzicka T, Donhauser G, Linke RP, et al. [Cutaneous amyloidoses]. Hautarzt. May 1990;41(5):245-55. [Medline].
Sawamura D, Sato-Matsumura KC, Shibaki A, et al. A case of lichen amyloidosis treated with pulsed dye laser. J Eur Acad Dermatol Venereol. Mar 2005;19(2):262-3. [Medline].
Shanon J, Sagher F. Interscapular cutaneous amyloidosis. Arch Dermatol. Aug 1970;102(2):195-8. [Medline].
Shirahama T, Cohen AS. High-resolution electron microscopic analysis of the amyloid fibril. J Cell Biol. Jun 1967;33(3):679-708. [Medline].
Vestey JP, Tidman MJ, Mclaren KM. Primary nodular cutaneous amyloidosis--long-term follow-up and treatment. Clin Exp Dermatol. Mar 1994;19(2):159-62. [Medline].
Weyers W, Weyers I, Bonczkowitz M, et al. Lichen amyloidosus: a consequence of scratching. J Am Acad Dermatol. Dec 1997;37(6):923-8. [Medline].
Wolf M, Tolmach JA. Macular amyloidosis. Arch Dermatol. Mar 1969;99(3):373-4. [Medline].
Yamagihara M, Kitajima Y, Yaoita H. Ultrastructural observation of the relationship between amyloid filaments and half desmosomes in macular amyloidosis [abstract]. J Cutan Pathol. 1980;7:7:213.
al-Ratrout JT, Satti MB. Primary localized cutaneous amyloidosis: a clinicopathologic study from Saudi Arabia. Int J Dermatol. Jun 1997;36(6):428-34. [Medline].
de Argila D, Ortiz-Romero PL, Ortiz-Frutos J, et al. Cutaneous macular amyloidosis associated with multiple endocrine neoplasia 2A. Clin Exp Dermatol. Jul 1996;21(4):313-4. [Medline].
Further Reading
Keywords
macular amyloidosis, amyloid, amyloid-P, serum amyloid-P, SAP, Sipple syndrome, MA
