eMedicine Specialties > Dermatology > Metabolic Diseases

Amyloidosis, Lichen

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: Nov 6, 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, 7.5-10 nm thick of indefinite length arranged in a loose meshwork.

X-ray diffraction crystallography and infrared spectroscopy revealed that these fibrils have a meridional, antiparallel, beta-pleated sheet configuration with polypeptide chains arranged perpendicular to the long axis of the fibrils.1

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.

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

Lichen amyloidosis has been reported in association with few syndromes. The most intriguing is the association with multiple endocrine neoplasia type 2A (MEN 2A), also known as Sipple syndrome.2,3,4,5,6,7,8,9,10 The cardinal triad of this autosomal dominant syndrome is medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. Many cases of familial lichen amyloidosis were reported in families with MEN 2A. The lichen amyloidosis in this syndrome is usually localized to the interscapular region consisting of lichenoid papules, with hyperpigmentation and fine scaling. The histopathologic and immunohistochemistry findings are similar to those in isolated lichen amyloidosis, pointing to keratin-derived amyloidosis.

A single case of lichen amyloidosis in Alagille syndrome has been reported.11 This consists of interlobular biliary duct deficiency and cardiovascular, vertebral, and ocular anomalies.
The disease is associated with marked pruritus secondary to cholestasis. This is believed to be the cause of the amyloid deposition.

Maddison et al suggest a possible cause of the severe pruritus associated with lichen amyloidosis in relation to nerve fiber density. They suggest the hypersensitivity of the remaining nerve fibers is a response to an unexplained neurodegeneration of the absent nerve fibers.12

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.13 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.

Weyers et al presented a convincing argument that the deposition of amyloid in lichen amyloidosis is not the cause but the result of itching and scratching. This argument was based on several lines of evidence.14

Amyloid deposition per se does not cause itching. Systemic amyloidosis is not associated with pruritus. Nonpruritic lichen amyloidosis has also been described. Pruritus usually precedes the development of lichen amyloidosis by years. Amyloid cannot be detected in clinically healthy skin of patients with lichen amyloidosis.

Striking similarities, both clinically and histopathologically, exist between lichen amyloidosis and lichen simplex chronicus.

Race

Lichen amyloidosis is believed to be more common in persons of Chinese ancestry than in other people.

Sex

Lichen amyloidosis is more common in males than in females.

Age

Lichen amyloidosis occurs most frequently in persons aged 50-60 years.

Clinical

History

Typically, lichen amyloidosis is an intensely itchy eruption.

Physical

Lichen amyloidosis presents as intensely pruritic, red-brown hyperkeratotic papules most commonly seen on the pretibial surfaces, but it can also occur on the feet and the thighs.

Causes

See Pathophysiology.

More on Amyloidosis, Lichen

Overview: Amyloidosis, Lichen
Differential Diagnoses & Workup: Amyloidosis, Lichen
Treatment & Medication: Amyloidosis, Lichen
References
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References

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

  2. Bugalho MJ, Limbert E, Sobrinho LG, et al. A kindred with multiple endocrine neoplasia type 2A associated with pruritic skin lesions. Cancer. Dec 1 1992;70(11):2664-7. [Medline].

  3. Chabre O, Labat F, Pinel N, Berthod F, Tarel V, Bachelot I. Cutaneous lesion associated with multiple endocrine neoplasia type 2A: lichen amyloidosis or notalgia paresthetica?. Henry Ford Hosp Med J. 1992;40(3-4):245-8. [Medline].

  4. Gagel RF, Levy ML, Donovan DT, Alford BR, Wheeler T, Tschen JA. Multiple endocrine neoplasia type 2a associated with cutaneous lichen amyloidosis. Ann Intern Med. Nov 15 1989;111(10):802-6. [Medline].

  5. Kousseff BG, Espinoza C, Zamore GA. Sipple syndrome with lichen amyloidosis as a paracrinopathy: pleiotropy, heterogeneity, or a contiguous gene?. J Am Acad Dermatol. Oct 1991;25(4):651-7. [Medline].

  6. Kousseff BG. Multiple endocrine neoplasia 2 (MEN 2)/MEN 2A (Sipple syndrome). Dermatol Clin. Jan 1995;13(1):91-7. [Medline].

  7. Nunziata V, di Giovanni G, Lettera AM, D'Armiento M, Mancini M. Cutaneous lichen amyloidosis associated with multiple endocrine neoplasia type 2A. Henry Ford Hosp Med J. 1989;37(3-4):144-6. [Medline].

  8. Pacini F, Fugazzola L, Bevilacqua G, Viacava P, Nardini V, Martino E. Multiple endocrine neoplasia type 2A and cutaneous lichen amyloidosis: description of a new family. J Endocrinol Invest. Apr 1993;16(4):295-6. [Medline].

  9. Robinson MF, Furst EJ, Nunziata V, et al. Characterization of the clinical features of five families with hereditary primary cutaneous lichen amyloidosis and multiple endocrine neoplasia type 2. Henry Ford Hosp Med J. 1992;40(3-4):249-52. [Medline].

  10. Rothberg AE, Raymond VM, Gruber SB, Sisson J. Familial medullary thyroid carcinoma associated with cutaneous lichen amyloidosis. Thyroid. Jun 2009;19(6):651-5. [Medline].

  11. Doutre MS, Beylot C, Couzigou P, Beraud C. Lichen amyloidosis in Alagille syndrome. Arch Dermatol. Oct 1991;127(10):1590-1. [Medline].

  12. Maddison B, Namazi MR, Samuel LS, et al. Unexpected diminished innervation of epidermis and dermoepidermal junction in lichen amyloidosus. Br J Dermatol. Aug 2008;159(2):403-6. [Medline].

  13. 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].

  14. 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].

  15. Frolich M, Enk A, Diepgen TL, Weisshaar E. Successful treatment of therapy-resistant pruritus in lichen amyloidosis with menthol. Acta Derm Venereol. 2009;89(5):524-6. [Medline].

  16. Castanedo-Cazares JP, Lepe V, Moncada B. Lichen amyloidosis improved by 0.1% topical tacrolimus. Dermatology. 2002;205(4):420-1. [Medline].

  17. 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].

  18. 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].

  19. 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].

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

  21. Aram H. Failure of etretinate (RO 10-9359) in lichen amyloidosus. Int J Dermatol. Apr 1986;25(3):206. [Medline].

  22. David M, Ingber A, Ben-Chetrit A, Sandbank J, Sandbank M. Effect of etretinate on lichen amyloidosus. Dermatologica. 1987;175(6):302-3. [Medline].

  23. Marschalko M, Daroczy J, Soos G. Etretinate for the treatment of lichen amyloidosis. Arch Dermatol. May 1988;124(5):657-9. [Medline].

  24. Choi JY, Sippe J, Lee S. Acitretin for lichen amyloidosus. Australas J Dermatol. May 2008;49(2):109-13. [Medline].

  25. 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].

  26. Parsi K, Kossard S. Thermosensitive lichen amyloidosis. Int J Dermatol. Dec 2004;43(12):925-8. [Medline].

  27. Aoki M, Kawana S. Lichen amyloidosis of the auricular concha: successful treatment with electrodesiccation. J Dermatol. Feb 2009;36(2):116-7. [Medline].

  28. 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].

  29. 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].

  30. 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].

  31. 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].

  32. Kuligowski ME, Chang A. Non-itchy lichen amyloidosus. Int J Dermatol. Oct 1992;31(10):747. [Medline].

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

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

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

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

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

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

  39. Touart DM, Sau P. Cutaneous deposition diseases. Part I. J Am Acad Dermatol. Aug 1998;39(2 Pt 1):149-71; quiz 172-4. [Medline].

  40. Wang WJ. Clinical features of cutaneous amyloidoses. Clin Dermatol. Apr-Jun 1990;8(2):13-9. [Medline].

  41. Wong CK. Lichen amyloidosus. A relatively common skin disorder in Taiwan. Arch Dermatol. Sep 1974;110(3):438-40. [Medline].

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Further Reading

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Keywords

lichen amyloidosis, LA, amyloid deposits, multiple endocrine neoplasia type 2A, MEN 2A, Sipple syndrome

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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.

 
 
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