eMedicine Specialties > Dermatology > Metabolic Diseases

Amyloidosis, Macular

Author: Sultan Al-Khenaizan, MBBS, FRCP(C), Consulting Staff, Departments of Dermatology and Internal Medicine, King Fahad National Guard Hospital, Saudi Arabia
Contributor Information and Disclosures

Updated: Sep 25, 2009

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.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.

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.

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.4,5 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.6

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.

Clinical

History

Macular amyloidosis is a pruritic eruption that is variable in severity. Frequently, patients seek medical attention because of the hyperpigmentation.

Physical

Macular amyloidosis 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.

Reddish brown patch on the back characteristic of...

Reddish brown patch on the back characteristic of macular amyloidosis. Courtesy of Hon Pak, MD, and reviewed by Ross Levy, MD.

[ CLOSE WINDOW ]
Reddish brown patch on the back characteristic of...

Reddish brown patch on the back characteristic of macular amyloidosis. Courtesy of Hon Pak, MD, and reviewed by Ross Levy, MD.


Another patient with macular amyloidosis on the b...

Another patient with macular amyloidosis on the back. Courtesy of Hon Pak, MD, and reviewed by Ross Levy, MD.

[ CLOSE WINDOW ]
Another patient with macular amyloidosis on the b...

Another patient with macular amyloidosis on the back. Courtesy of Hon Pak, MD, and reviewed by Ross Levy, MD.


Although a reticulated or rippled pattern of pigmentation has been emphasized as a characteristic and diagnostic feature of macular amyloidosis, in 2 case series, less than 50% of patients had this feature.

Reticulated pattern of pigmentation on the should...

Reticulated pattern of pigmentation on the shoulder of a patient with macular amyloidosis. Courtesy of Hon Pak, MD, and reviewed by Ross Levy, MD.

[ CLOSE WINDOW ]
Reticulated pattern of pigmentation on the should...

Reticulated pattern of pigmentation on the shoulder of a patient with macular amyloidosis. Courtesy of Hon Pak, MD, and reviewed by Ross Levy, MD.


Close-up of the above patient's eruption. Courtes...

Close-up of the above patient's eruption. Courtesy of Hon Pak, MD, and reviewed by Ross Levy, MD.

[ CLOSE WINDOW ]
Close-up of the above patient's eruption. Courtes...

Close-up of the above patient's eruption. Courtesy of Hon Pak, MD, and reviewed by Ross Levy, MD.


Causes

Constant friction and rubbing with a nylon brush or towel may cause macular amyloidosis.7

More on Amyloidosis, Macular

Overview: Amyloidosis, Macular
Differential Diagnoses & Workup: Amyloidosis, Macular
Treatment & Medication: Amyloidosis, Macular
Follow-up: Amyloidosis, Macular
Multimedia: Amyloidosis, Macular
References
[ CLOSE WINDOW ]

References

  1. Shirahama T, Cohen AS. High-resolution electron microscopic analysis of the amyloid fibril. J Cell Biol. Jun 1967;33(3):679-708. [Medline].

  2. Li JJ, McAdam KP. Human amyloid P component: an elastase inhibitor. Scand J Immunol. Sep 1984;20(3):219-26. [Medline].

  3. Apaydin R, Gurbuz Y, Bayramgurler D, Muezzinoglu B, Bilen N. Cytokeratin expression in lichen amyloidosus and macular amyloidosis. J Eur Acad Dermatol Venereol. May 2004;18(3):305-9. [Medline].

  4. Hashimoto K, Kobayashi H. Histogenesis of amyloid in the skin. Am J Dermatopathol. Summer 1980;2(2):165-71. [Medline].

  5. Hashimoto K, Ito K, Kumakiri M, Headington J. Nylon brush macular amyloidosis. Arch Dermatol. May 1987;123(5):633-7. [Medline].

  6. 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.

  7. Weyers W, Weyers I, Bonczkowitz M, Diaz-Cascajo C, Schill WB. Lichen amyloidosus: a consequence of scratching. J Am Acad Dermatol. Dec 1997;37(6):923-8. [Medline].

  8. Ostovari N, Mohtasham N, Oadras MS, Malekzad F. 532-nm and 1064-nm Q-switched Nd:YAG laser therapy for reduction of pigmentation in macular amyloidosis patches. J Eur Acad Dermatol Venereol. Apr 2008;22(4):442-6. [Medline]. [Full Text].

  9. 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].

  10. Monfrecola G, Iandoli R, Bruno G, Martellotta D. Lichen amyloidosus: a new therapeutic approach. Acta Derm Venereol. 1985;65(5):453-5. [Medline].

  11. Ozkaya-Bayazit E, Kavak A, Gungor H, Ozarmagan G. Intermittent use of topical dimethyl sulfoxide in macular and papular amyloidosis. Int J Dermatol. Dec 1998;37(12):949-54. [Medline].

  12. Lim KB, Tan SH, Tan KT. Lack of effect of dimethyl sulphoxide (DMSO) on amyloid deposits in lichen amyloidosis. Br J Dermatol. Sep 1988;119(3):409-10. [Medline].

  13. Pandhi R, Kaur I, Kumar B. Lack of effect of dimethylsulphoxide in cutaneous amyloidosis. J Dermatolog Treat. Mar 2002;13(1):11-4. [Medline].

  14. Sawamura D, Sato-Matsumura KC, Shibaki A, Akiyama M, Kikuchi T, Shimizu H. A case of lichen amyloidosis treated with pulsed dye laser. J Eur Acad Dermatol Venereol. Mar 2005;19(2):262-3. [Medline].

  15. 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].

  16. 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].

  17. 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].

  18. Breathnach SM. Amyloid and amyloidosis. J Am Acad Dermatol. Jan 1988;18(1 Pt 1):1-16. [Medline].

  19. Breathnach SM, Bhogal B, Dyck RF, De Beer FC, Black MM, Pepys MB. 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].

  20. 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].

  21. Brownstein MH, Hashimoto K, Greenwald G. Biphasic amyloidosis: link between macular and lichenoid forms. Arch Dermatol. Sep 1972;106(3):419. [Medline].

  22. Cortes A. Primary cutaneous amyloidosis. Dermatologica. 1969;139(2):109-14. [Medline].

  23. de Argila D, Ortiz-Romero PL, Ortiz-Frutos J, Rodriguez-Peralto JL, Iglesias L. Cutaneous macular amyloidosis associated with multiple endocrine neoplasia 2A. Clin Exp Dermatol. Jul 1996;21(4):313-4. [Medline].

  24. Eanes ED, Glenner GG. X-ray diffraction studies on amyloid filaments. J Histochem Cytochem. Nov 1968;16(11):673-7. [Medline].

  25. 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].

  26. 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].

  27. Horiguchi Y, Fine JD, Leigh IM, Yoshiki T, Ueda M, Imamura S. Lamina densa malformation involved in histogenesis of primary localized cutaneous amyloidosis. J Invest Dermatol. Jul 1992;99(1):12-8. [Medline].

  28. Hudson LD. Macular amyloidosis: treatment with ultraviolet B. Cutis. Jul 1986;38(1):61-2. [Medline].

  29. Kibbi AG, Rubeiz NG, Zaynoun ST, Kurban AK. Primary localized cutaneous amyloidosis. Int J Dermatol. Feb 1992;31(2):95-8. [Medline].

  30. 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].

  31. Kurban AK, Malak JA, Afifi AK, Mire J. Primary localized macular cutaneous amyloidosis: histochemistry and electron microscopy. Br J Dermatol. Jul 1971;85(1):52-60. [Medline].

  32. Lambert WC. Cutaneous deposition disorders. In: Farmer ER, Hood AF, eds. Pathology of the Skin. Norwalk, Conn: Appleton & Lange; 1990:432-50.

  33. Macular amyloidosis. Arch Dermatol. Mar 1969;99(3):373-4. [Medline].

  34. Piette WW. Myeloma, paraproteinemias, and the skin. Med Clin North Am. Jan 1986;70(1):155-76. [Medline].

  35. Ruzicka T, Donhauser G, Linke RP, Landthaler M, Bieber T. [Cutaneous amyloidoses]. Hautarzt. May 1990;41(5):245-55. [Medline].

  36. Shanon J, Sagher F. Interscapular cutaneous amyloidosis. Arch Dermatol. Aug 1970;102(2):195-8. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

amyloidosis, macular amyloidosis, amyloid, amyloid-P, serum amyloid-P, SAP, Sipple syndrome, MA

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Sultan Al-Khenaizan, MBBS, FRCP(C), Consulting Staff, Departments of Dermatology and Internal Medicine, King Fahad National Guard Hospital, Saudi Arabia
Disclosure: Nothing to disclose.

Medical Editor

Catharine Lisa Kauffman, MD, FACP, Georgetown Dermatology and Georgetown Dermpath
Catharine Lisa Kauffman, MD, FACP is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Royal Society of Medicine, Society for Investigative Dermatology, and Women's Dermatologic Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Warren R Heymann, MD, Head, Division of Dermatology, Professor, Department of Internal Medicine, University of Medicine and Dentistry of New Jersey
Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.