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Primary Localized Cutaneous Amyloidosis of Keratinocyte Origin: An Update with Emphasis on Atypical Clinical Variants

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Abstract

Amyloid is a protein derived from at least 20 different substances. Once misfolded, it results in a group of cutaneous and systemic conditions. Primary localized cutaneous amyloidosis of keratinocyte origin is a very common subtype that can manifest either as lichen or macular amyloidosis, lacking systemic involvement. Lichen amyloidosis often presents as multiple hyperpigmented papules on the lower extremities whereas macular amyloidosis is classically characterized by dark brown rippled macules on the interscapular area. Review of the literature reveals that in addition to the classical presentation of primary localized cutaneous amyloidosis there exists a plethora of various manifestations that can be grouped into either geographic or morphologic categories. This review provides clinicians with the intimate knowledge of these presentations and summarizes the available treatment modalities.

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References

  1. Kaltoft B, Schmidt G, Lauritzen AF, et al. Primary localised cutaneous amyloidosis: a systematic review. Dan Med J. 2013;60(11):A4727.

    PubMed  Google Scholar 

  2. Fernandez-Flores A. Cutaneous amyloidosis: a concept review. Am J Dermatopathol. 2012;34(1):1–14 (quiz 15–7).

    Article  PubMed  Google Scholar 

  3. Lu P, Wu FF, Rong ZL, et al. Clinical and genetic features of Chinese patients with lichen and macular primary localized cutaneous amyloidosis. Clin Exp Dermatol. 2019;44(4):e110–7.

    Article  PubMed  CAS  Google Scholar 

  4. Ueo D, Utani A, Okubo Y, et al. Familial primary localized cutaneous amyloidosis in a Japanese family. J Dermatol Sci. 2016;83(2):162–4.

    Article  PubMed  Google Scholar 

  5. Wali A, Liu L, Takeichi T, et al. Familial primary localized cutaneous amyloidosis results from either dominant or recessive mutations in OSMR. Acta Derm Venereol. 2015;95(8):1005–7.

    Article  PubMed  CAS  Google Scholar 

  6. Adams R, Colmont C, Mukhtar A, et al. A novel oncostatin M/interleukin-31 receptor mutation in familial primary localized cutaneous amyloidosis. Clin Exp Dermatol. 2020;45(2):254–6.

    Article  PubMed  CAS  Google Scholar 

  7. Lin MW, Lee DD, Liu TT, et al. Novel IL31RA gene mutation and ancestral OSMR mutant allele in familial primary cutaneous amyloidosis. Eur J Hum Genet. 2010;18(1):26–32.

    Article  PubMed  CAS  Google Scholar 

  8. Weidner T, Illing T, Elsner P. Primary localized cutaneous amyloidosis: a systematic treatment review. Am J Clin Dermatol. 2017;18(5):629–42.

    Article  PubMed  Google Scholar 

  9. Ruzicka T, Mihara R. Anti-interleukin-31 receptor A antibody for atopic dermatitis. N Engl J Med. 2017;376(21):2093.

    PubMed  Google Scholar 

  10. Shiao YM, Chung HJ, Chen CC, et al. MCP-1 as an effector of IL-31 signaling in familial primary cutaneous amyloidosis. J Invest Dermatol. 2013;133(5):1375–8.

    Article  PubMed  CAS  Google Scholar 

  11. Groves RW. Amyloidosis. In: Bolognia JL, Schaffer JV, Cerroni L. editors. Dermatology. China. Elsevier Limited; 2018. pp. 754–763.e1.

  12. Verga U, Fugazzola L, Cambiaghi S, et al. Frequent association between MEN 2A and cutaneous lichen amyloidosis. Clin Endocrinol (Oxf). 2003;59(2):156–61.

    Article  CAS  Google Scholar 

  13. Scapineli JO, Ceolin L, Puñales MK, et al. MEN 2A-related cutaneous lichen amyloidosis: report of three kindred and systematic literature review of clinical, biochemical and molecular characteristics. Fam Cancer. 2016;15(4):625–33.

    Article  PubMed  CAS  Google Scholar 

  14. Wang WJ. Clinical features of cutaneous amyloidoses. Clin Dermatol. 1990;8(2):13–9.

    Article  PubMed  CAS  Google Scholar 

  15. Savk O, Savk E. Investigation of spinal pathology in notalgia paresthetica. J Am Acad Dermatol. 2005;52(6):1085–7.

    Article  PubMed  Google Scholar 

  16. Callender VD, St-Surin Lord S, Davis LEC, Maclin M. Postinflammatory hyperpigmentation etiologic and therapeutic considerations. Am J Clin Dermatol. 2011;12(2):87–99.

    Article  PubMed  Google Scholar 

  17. Wagner G, Rose C, Sachse MM. Clinical variants of lichen planus. J Dtsch Dermatol Ges. 2013;11(4):309–19.

    PubMed  Google Scholar 

  18. Leung N, Oliveira M, Selim MA, et al. Erythema dyschromicum perstans: a case report and systematic review of histologic presentation and treatment. Int J Womens Dermatol. 2018;4(4):216–22.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Dereure O. Drug-induced hyperpigmentation. Am J Clin Dermatol. 2001;2(3):253–62.

    Article  PubMed  CAS  Google Scholar 

  20. Mysore V, Malkud S, Anitha B. Frictional melanosis and its clinical and histopathological features. Iran J Dermatol. 2018;21:124–7.

    Google Scholar 

  21. Sisto K, Khachemoune A. Elephantiasis nostras verrucosa: a review. Am J Clin Dermatol. 2008;9(3):141–6.

    Article  PubMed  Google Scholar 

  22. Lotti T, Buggiani G, Prignano F. Prurigo nodularis and lichen simplex chronicus. Dermatol Ther. 2008;21:42–6.

    Article  PubMed  Google Scholar 

  23. Pourrabbani S, Marra DE, Iwasaki J, et al. Colloid milium: a review and update. J Drugs Dermatol. 2007;6(3):293–6.

    PubMed  Google Scholar 

  24. Wang WJ, Chang YT, Huang CY, et al. Clinical and histopathological characteristics of primary cutaneous amyloidosis in 794 Chinese patients. Zhonghua Yi Xue Za Zhi (Taipei). 2001;64(2):101–7.

    PubMed  CAS  Google Scholar 

  25. Breathnach SM. Amyloid and amyloidosis. J Am Acad Dermatol. 1988;18(1 Pt 1):1–16.

    Article  PubMed  CAS  Google Scholar 

  26. Garg T, Chander R, Jabeen M, et al. Amyloidosis cutis dyschromica: a rare pigmentary disorder. J Cutan Pathol. 2011;38(10):823–6.

    PubMed  Google Scholar 

  27. Belli AA, Kara A, Dere Y, et al. Association of amyloidosis cutis dyschromica and familial Mediterranean fever. An Bras Dermatol. 2017;92(5 Suppl. 1):21–3.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Yang CF, Lin SP, Chiang CP, et al. Loss of GPNMB causes autosomal-recessive amyloidosis cutis dyschromica in humans. Am J Hum Genet. 2018;102(2):219–32.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Wang J, Li Y, Xing L, et al. Three novel mutations in GPNMB in two pedigrees with amyloidosis cutis dyschromica. Br J Dermatol. 2019;181(6):1327–9.

    Article  PubMed  CAS  Google Scholar 

  30. Urabe K, Hori Y. Dyschromatosis. Semin Cutan Med Surg. 1997;16(1):81–5.

    Article  PubMed  CAS  Google Scholar 

  31. Lehmann AR, McGibbon D, Stefanini M. Xeroderma pigmentosum. Orphanet J Rare Dis. 2011;6:70.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Garg T, Marak A, Ahmed R, et al. An unusual presentation of primary cutaneous amyloidosis. Dermatol Online J. 2017;23(8):7.

    Article  Google Scholar 

  33. Ho MH, Chong LY. Poikiloderma-like cutaneous amyloidosis in an ethnic Chinese girl. J Dermatol. 1998;25(11):730–4.

    Article  PubMed  CAS  Google Scholar 

  34. Mahajan VK, Chauhan PS, Mehta KS, et al. Poikiloderma vasculare atrophicans: a distinct clinical entity? Indian J Dermatol. 2015;60(2):216.

    PubMed  PubMed Central  Google Scholar 

  35. Nashan D, Faulhaber D, Ständer S, et al. Mycosis fungoides: a dermatological masquerader. Br J Dermatol. 2007;156(1):1–10.

    Article  PubMed  CAS  Google Scholar 

  36. Cho TH, Lee MH. A case of lichen amyloidosus accompanied by vesicles and dyschromia. Clin Exp Dermatol. 2008;33(3):291–3.

    Article  PubMed  Google Scholar 

  37. Suranagi VV, Siddramappa B, Bannur HB, et al. Bullous variant of familial biphasic lichen amyloidosis: a unique combination of three rare presentations. Indian J Dermatol. 2015;60(1):105.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Chandran NS, Goh B-K, Lee S-S, et al. Case of primary localized cutaneous amyloidosis with protean clinical manifestations: lichen, poikiloderma-like, dyschromic and bullous variants. J Dermatol. 2011;38(11):1066–71.

    Article  PubMed  Google Scholar 

  39. Wu JJ, Su YN, Hsiao CH, et al. Macular amyloidosis presenting in an incontinentia pigmenti-like pattern with subepidermal blister formation. J Eur Acad Dermatol Venereol. 2008;22(5):635–7.

    Article  PubMed  CAS  Google Scholar 

  40. Partington MW, Marriott PJ, Prentice RS, et al. Familial cutaneous amyloidosis with systemic manifestations in males. Am J Med Genet. 1981;10(1):65–75.

    Article  PubMed  CAS  Google Scholar 

  41. Wan H, Ran Y. Unusual primary cutaneous amyloidosis with an incontinentia pigmenti-like pattern. Int J Dermatol. 2011;50(4):485–7.

    Article  PubMed  Google Scholar 

  42. Eng AM. Familial macular amyloidosis masquerading as incontinentia pigmenti. Arch Dermatol. 1977;113(5):694–5.

    Google Scholar 

  43. An HT, Han KH, Cho KH. Macular amyloidosis with an incontinentia pigmenti-like pattern. Br J Dermatol. 2000;142(2):371–3.

    Article  PubMed  CAS  Google Scholar 

  44. Abbas O, Ugent S, Borirak K, et al. Linear macular amyloidosis. J Eur Acad Dermatol Venereol. 2009;23(12):1446–8.

    Article  PubMed  CAS  Google Scholar 

  45. Black MM, Maibach HI. Macular amyloidosis simulating naevoid hyperpigmentation. Br J Dermatol. 1974;90(4):461–4.

    Article  PubMed  CAS  Google Scholar 

  46. Cornejo KM, Lagana FJ, Deng A. Nodular amyloidosis derived from keratinocytes: an unusual type of primary localized cutaneous nodular amyloidosis. Am J Dermatopathol. 2015;37(11):e129–33.

    Article  PubMed  Google Scholar 

  47. Mitteldorf C, Kempf W. Cutaneous pseudolymphoma. Surg Pathol. 2017;10(2):455–76.

    Article  Google Scholar 

  48. Ishak R, Kurban M, Kibbi AG, et al. Cutaneous sarcoidosis: clinicopathologic study of 76 patients from Lebanon. Int J Dermatol. 2015;54(1):33–41.

    Article  PubMed  Google Scholar 

  49. Thornsberry LA, English JC 3rd. Etiology, diagnosis, and therapeutic management of granuloma annulare: an update. Am J Clin Dermatol. 2013;14(4):279–90.

    Article  PubMed  Google Scholar 

  50. Shimauchi T, Shin JH, Tokura Y. Primary cutaneous amyloidosis of the auricular concha: case report and review of published work. J Dermatol. 2006;33(2):128–31.

    Article  PubMed  Google Scholar 

  51. Weyers W, Weyers I, Bonczkowitz M, et al. Lichen amyloidosus: a consequence of scratching. J Am Acad Dermatol. 1997;37(6):923–8.

    Article  PubMed  CAS  Google Scholar 

  52. Wenson SF, Jessup CJ, Johnson MM, et al. Primary cutaneous amyloidosis of the external ear: a clinicopathological and immunohistochemical study of 17 cases. J Cutan Pathol. 2012;39(2):263–9.

    Article  PubMed  Google Scholar 

  53. Wang WJ, Huang CY, Chang YT, et al. Anosacral cutaneous amyloidosis: a study of 10 Chinese cases. Br J Dermatol. 2000;143(6):1266–9.

    Article  PubMed  CAS  Google Scholar 

  54. Liu HN, Wang WJ, Chen CC, et al. Senile gluteal dermatosis: a clinicopathologic study of 12 cases and its distinction from anosacral amyloidosis. J Eur Acad Dermatol Venereol. 2012;26(2):258–60.

    Article  PubMed  CAS  Google Scholar 

  55. Liu C, Ding L-J, Tan C. Brownish macules on the right temple. J Cosmet Dermatol. 2020;19(6):1479–80.

    Article  PubMed  Google Scholar 

  56. Lee JY, Park MY, Ahn J. A case of lichen amyloidosis improved by topical salicylic acid and topical corticosteroid. Korean J Dermatol. 2010;48:533–6.

    Google Scholar 

  57. Pepys MB, Herbert J, Hutchinson WL, et al. Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. Nature. 2002;417(6886):254–9.

    Article  PubMed  CAS  Google Scholar 

  58. Nocchi L, Roy N, D'Attilia M, et al. Interleukin-31-mediated photoablation of pruritogenic epidermal neurons reduces itch-associated behaviours in mice. Nat Biomed Eng. 2019;3(2):114–25.

    Article  PubMed  CAS  Google Scholar 

  59. Kurian SS, Rai R, Madhukar ST. Amyloidosis cutis dyschromica. Indian Dermatol Online J. 2013;4(4):344–6.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Schreml S, Szeimies RM, Vogt T, et al. Cutaneous amyloidoses and systemic amyloidoses with cutaneous involvement. Eur J Dermatol. 2010;20(2):152–60.

    Article  PubMed  Google Scholar 

  61. Mahon C, Oliver F, Purvis D, et al. Amyloidosis cutis dyschromica in two siblings and review of the epidemiology, clinical features and management in 48 cases. Australas J Dermatol. 2016;57(4):307–11.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  63. Chakravarty K, Chanda M. Role of colchicine in primary localised cutaneous amyloidosis. Indian J Dermatol Venereol Leprol. 1995;61(5):268–9.

    PubMed  CAS  Google Scholar 

  64. Akar A, Tastan HB, Demiriz M, Erbil H. Lack of effect of cyclosporine in lichen amyloidosis associated with atopic dermatitis. Eur J Dermatol. 2002;12(6):612–4.

    PubMed  Google Scholar 

  65. Ozcan A, Senol M, Aydin NE, et al. Amyloidosis cutis dyschromica: a case treated with acitretin. J Dermatol. 2005;32(6):474–7.

    Article  PubMed  Google Scholar 

  66. Wang M, Lin Y, Wu W, et al. Treatment of lichen amyloidosis with fractional CO2 laser and topical steroid: a preliminary study of 10 cases. Lasers Med Sci. 2021;36(5):1123–7.

    Article  PubMed  Google Scholar 

  67. Ma H, Su X, Zhu G, et al. Primary localized cutaneous amyloidosis with lichen and poikiloderma-like lesions and an excellent response to systemic acitretin. An Bras Dermatol. 2016;91(5):661–3.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Al Yahya RS. Treatment of primary cutaneous amyloidosis with laser: a review of the literature. Lasers Med Sci. 2016;31(5):1027–35.

    Article  PubMed  Google Scholar 

  69. Sobhi RM, Sharaoui I, El Nabarawy EA, et al. Comparative study of fractional CO2 laser and fractional CO2 laser-assisted drug delivery of topical steroid and topical vitamin C in macular amyloidosis. Lasers Med Sci. 2018;33(4):909–16.

    Article  PubMed  Google Scholar 

  70. Sawamura D, Shibaki A, Akiyama M, et al. A case of lichen amyloidosis treated with pulsed dye laser. J Eur Acad Dermatol Venereol. 2005;19:262–3.

    Article  PubMed  CAS  Google Scholar 

  71. Barsky M, Buka RL. Pulsed dye laser for the treatment of macular amyloidosis: a case report. Cutis. 2014;93(4):189–92.

    PubMed  Google Scholar 

  72. Yuksek J, Sezer E, Aksu M, Erkokmaz U. Transcutaneous electrical nerve stimulation for reduction of pruritus in macular amyloidosis and lichen simplex. J Dermatol. 2011;38(6):546–52.

    Article  PubMed  Google Scholar 

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  1. Lamiaa Hamie, Isabelle Haddad have equally contributed as first authors.

Authors and Affiliations

  1. Department of Dermatology, American University of Beirut Medical Center, Riad El Solh/Beirut, P.O. Box 11-0236, Beirut, 1107 2020, Lebanon

    Lamiaa Hamie, Isabelle Haddad, Nourhane Nasser, Mazen Kurban & Ossama Abbas

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  1. Lamiaa Hamie
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  2. Isabelle Haddad
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  3. Nourhane Nasser
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Correspondence to Ossama Abbas.

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Lamiaa Hamie, Isabelle Haddad, Nourhane Nasser, Mazen Kurban, and Ossama Abbas have no conflicts of interest that are directly relevant to the content of this article.

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LH, OA, and IH planned the study. LH, IH, NN, and OA contributed to the writing of the manuscript. LH, IH, NN, OA, and MK were responsible for reviewing the manuscript. LH, IH, and OA created the figures and tables. LH and OA submitted the manuscript.

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Hamie, L., Haddad, I., Nasser, N. et al. Primary Localized Cutaneous Amyloidosis of Keratinocyte Origin: An Update with Emphasis on Atypical Clinical Variants. Am J Clin Dermatol 22, 667–680 (2021). https://doi.org/10.1007/s40257-021-00620-9

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