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Kutane Amyloidosen

Cutaneous amyloidosis

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Zusammenfassung

Amyloide sind in der Natur weit verbreitete Proteinaggregate mit teils krankheitsauslösenden, vielfach aber auch wichtigen biologischen Funktionen. Obwohl die Ultrastruktur von Amyloid extrem konserviert ist, bleibt der Mechanismus der Amyloidogenese weiterhin ein komplexes Forschungsfeld. Beim Menschen können Amyloidosen primär in der Haut entstehen oder diese sekundär betreffen. Eine akkurate Diagnostik ist entscheidend für die Therapieplanung dieser heterogenen Gruppe an Krankheitsentitäten. Daher gibt diese Arbeit zunächst eine Übersicht über die verschiedenen Formen der Amyloidosen, um dann auf Diagnostik und mögliche Therapieoptionen einzugehen. Weiterhin wird die Unterscheidung zwischen funktionellen und krankheitsauslösenden Amyloiden vorgestellt.

Abstract

Amyloids are common protein aggregates in nature. Some amyloids fulfill important biological tasks while others are known to cause diseases. Despite the fact that the ultrastructure of amyloid is highly conserved, the mechanism of amyloidogenesis remains a challenging research topic. In humans, amyloidoses may develop in the skin or lead to skin signs due to secondary cutaneous involvement. An accurate diagnostic procedure is crucial for planning the therapy of this heterogeneous group of diseases. Therefore, the aim of this paper is to give an overview on the different kinds of amyloidoses as well as on diagnostic and therapeutic approaches. Furthermore, the discrimination between functional and disease-causing amyloid is briefly presented.

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Literatur

  1. Albers SE, Fenske NA, Glass LF et al (1994) Atypical beta 2-microglobulin amyloidosis following short-term hemodialysis. Am J Dermatopathol 16:179–184

    Article  CAS  PubMed  Google Scholar 

  2. Alster TS, Manaloto RM (1999) Nodular amyloidosis treated with a pulsed dye laser. Dermatol Surg 25:133–135

    Article  CAS  PubMed  Google Scholar 

  3. Alvarez-Lobos M, Hunter B, Cofre C et al (2006) Tumor necrosis factor receptor associated periodic syndrome (TRAPS). Report of two cases. Rev Med Chil 134:1558–1561

    PubMed  Google Scholar 

  4. Arbustini E, Verga L, Concardi M et al (2002) Electron and immuno-electron microscopy of abdominal fat identifies and characterizes amyloid fibrils in suspected cardiac amyloidosis. Amyloid 9:108–114

    CAS  PubMed  Google Scholar 

  5. Arita K, South AP, Hans-Filho G et al (2008) Oncostatin M receptor-beta mutations underlie familial primary localized cutaneous amyloidosis. Am J Hum Genet 82:73–80

    Article  CAS  PubMed  Google Scholar 

  6. Babilas P, Fiebig BS, Aslanidis C et al (2009) Identification of an oncostatin M receptor mutation associated with familial primary cutaneous amyloidosis. Br J Dermatol 161:944–947

    Article  CAS  PubMed  Google Scholar 

  7. Badtke MP, Hammer ND, Chapman MR (2009) Functional amyloids signal their arrival. Sci Signal 2:pe43

    Article  PubMed  Google Scholar 

  8. Bellotti V, Chiti F (2008) Amyloidogenesis in its biological environment: challenging a fundamental issue in protein misfolding diseases. Curr Opin Struct Biol 18:771–779

    Article  CAS  PubMed  Google Scholar 

  9. Bhak G, Choe YJ, Paik SR (2009) Mechanism of amyloidogenesis: nucleation-dependent fibrillation versus double-concerted fibrillation. BMB Rep 42:541–551

    CAS  PubMed  Google Scholar 

  10. Bozikov K, Janezic T (2006) Excision and split thickness skin grafting in the treatment of nodular primary localized cutaneous amyloidosis. Eur J Dermatol 16:315–316

    PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  12. Breathnach SM, Hintner H (1990) Amyloid P-component and the skin. Clin Dermatol 8:46–54

    Article  CAS  PubMed  Google Scholar 

  13. Brownstein MH, Helwig EB (1971) Secondary systemic amyloidosis: analysis of underlying disorders. South Med J 64:491–496

    CAS  PubMed  Google Scholar 

  14. Das J, Gogoi RK (2003) Treatment of primary localised cutaneous amyloidosis with cyclophosphamide. Indian J Dermatol Venereol Leprol 69:163–164

    CAS  PubMed  Google Scholar 

  15. Eder L, Bitterman H (2007) Image in clinical medicine. Amyloid purpura. N Engl J Med 356:2406

    Article  CAS  PubMed  Google Scholar 

  16. Eisenberg D, Nelson R, Sawaya MR et al (2006) The structural biology of protein aggregation diseases: fundamental questions and some answers. Acc Chem Res 39:568–575

    Article  CAS  PubMed  Google Scholar 

  17. Elimova E, Kisilevsky R, Ancsin JB (2009) Heparan sulfate promotes the aggregation of HDL-associated serum amyloid A: evidence for a proamyloidogenic histidine molecular switch. FASEB J 23:3436–3448

    Article  CAS  PubMed  Google Scholar 

  18. Ellis RJ, Minton AP (2006) Protein aggregation in crowded environments. Biol Chem 387:485–497

    Article  CAS  PubMed  Google Scholar 

  19. Fowler DM, Koulov AV, Balch WE, Kelly JW (2007) Functional amyloid–from bacteria to humans. Trends Biochem Sci 32:217–224

    Article  CAS  PubMed  Google Scholar 

  20. Gebbink MF, Claessen D, Bouma B et al (2005) Amyloids – a functional coat for microorganisms. Nat Rev Microbiol 3:333–341

    Article  CAS  PubMed  Google Scholar 

  21. Gerard S, Goff B le, Maugars Y et al (2007) Lasting remission of a Muckle-Wells syndrome with CIAS-1 mutation using half-dose anakinra. Joint Bone Spine 74:659

    Article  PubMed  Google Scholar 

  22. Glenner GG (1981) The bases of the staining of amyloid fibers: their physico-chemical nature and the mechanism of their dye-substrate interaction. Prog Histochem Cytochem 13:1–37

    CAS  PubMed  Google Scholar 

  23. Guo Z, Eisenberg D (2008) The structure of a fibril-forming sequence, NNQQNY, in the context of a globular fold. Protein Sci 17:1617–1623

    Article  CAS  PubMed  Google Scholar 

  24. Hammer ND, Wang X, McGuffie BA, Chapman MR (2008) Amyloids: friend or foe? J Alzheimers Dis 13:407–419

    CAS  PubMed  Google Scholar 

  25. Hashimoto K, Ito K, Taniguchi Y et al (1990) Keratin in cutaneous amyloidoses. Clin Dermatol 8:55–65

    Article  CAS  PubMed  Google Scholar 

  26. Hernandez-Nunez A, Dauden E, Moreno de Vega MJ et al (2001) Widespread biphasic amyloidosis: response to acitretin. Clin Exp Dermatol 26:256–259

    Article  CAS  PubMed  Google Scholar 

  27. Hobbs JR, Morgan AD (1963) Fluorescence microscopy with Thioflavine-T in the Diagnosis of amyloid. J Pathol Bacteriol 86:437–442

    Article  CAS  PubMed  Google Scholar 

  28. Iconomidou VA, Hamodrakas SJ (2008) Natural protective amyloids. Curr Protein Pept Sci 9:291–309

    Article  CAS  PubMed  Google Scholar 

  29. Inge-Vechtomov SG, Zhouravleva GA, Chernoff YO (2007) Biological roles of prion domains. Prion 1:228–235

    Article  PubMed  Google Scholar 

  30. Kimberley FC, Lobito AA, Siegel RM, Screaton GR (2007) Falling into TRAPS–receptor misfolding in the TNF receptor 1-associated periodic fever syndrome. Arthritis Res Ther 9:217

    Article  PubMed  Google Scholar 

  31. Kiuru-Enari S, Keski-Oja J, Haltia M (2005) Cutis laxa in hereditary gelsolin amyloidosis. Br J Dermatol 152:250–257

    Article  CAS  PubMed  Google Scholar 

  32. Kumakiri M, Hashimoto K (1979) Histogenesis of primary localized cutaneous amyloidosis: sequential change of epidermal keratinocytes to amyloid via filamentous degeneration. J Invest Dermatol 73:150–162

    Article  CAS  PubMed  Google Scholar 

  33. Landa G, Aloni E, Milshtein A et al (2004) Eyelid bleeding and atypical amyloidosis. Am J Ophthalmol 138:495–496

    Article  PubMed  Google Scholar 

  34. Li WM (1990) Histopathology of primary cutaneous amyloidoses and systemic amyloidosis. Clin Dermatol 8:30–35

    Article  CAS  PubMed  Google Scholar 

  35. Lien MH, Railan D, Nelson BR (1997) The efficacy of dermabrasion in the treatment of nodular amyloidosis. J Am Acad Dermatol 36:315–316

    Article  CAS  PubMed  Google Scholar 

  36. Love WE, Miedler JD, Smith MK et al (2008) The spectrum of primary cutaneous nodular amyloidosis: Two illustrative cases. J Am Acad Dermatol 58:S33–S35

    Article  PubMed  Google Scholar 

  37. Lundmark K, Westermark GT, Olsen A, Westermark P (2005) Protein fibrils in nature can enhance amyloid protein A amyloidosis in mice: cross-seeding as a disease mechanism. Proc Natl Acad Sci U S A 102:6098–6102

    Article  CAS  PubMed  Google Scholar 

  38. MacDonald DM, Black MM (1980) Secondary localized cutaneous amyloidosis in melanocytic naevi. Br J Dermatol 103:553–556

    Article  CAS  PubMed  Google Scholar 

  39. Maji SK, Perrin MH, Sawaya MR et al (2009) Functional amyloids as natural storage of peptide hormones in pituitary secretory granules. Science 325:328–332

    Article  CAS  PubMed  Google Scholar 

  40. Maji SK, Wang L, Greenwald J, Riek R (2009) Structure-activity relationship of amyloid fibrils. FEBS Lett 583:2610–2617

    Article  CAS  PubMed  Google Scholar 

  41. Malak JA, Smith EW (1962) Secondary localized cutaneous amyloidosis. Arch Dermatol 86:465–477

    CAS  PubMed  Google Scholar 

  42. Maurer-Stroh S, Debulpaep M, Kuemmerer N et al (2010) Exploring the sequence determinants of amyloid structure using position-specific scoring matrices. Nat Methods 7:237–242

    Article  CAS  PubMed  Google Scholar 

  43. McGlinchey RP, Shewmaker F, McPhie P et al (2009) The repeat domain of the melanosome fibril protein Pmel17 forms the amyloid core promoting melanin synthesis. Proc Natl Acad Sci U S A 106:13731–13736

    Article  CAS  PubMed  Google Scholar 

  44. Meretoja J (1969) Familial systemic paramyloidosis with lattice dystrophy of the cornea, progressive cranial neuropathy, skin changes and various internal symptoms. A previously unrecognized heritable syndrome. Ann Clin Res 1:314–324

    CAS  PubMed  Google Scholar 

  45. Mirault T, Launay D, Cuisset L et al (2006) Recovery from deafness in a patient with Muckle-Wells syndrome treated with anakinra. Arthritis Rheum 54:1697–1700

    Article  PubMed  Google Scholar 

  46. Muckle TJ (1979) The „Muckle-Wells“ syndrome. Br J Dermatol 100:87–92

    Article  CAS  PubMed  Google Scholar 

  47. Nelson R, Sawaya MR, Balbirnie M et al (2005) Structure of the cross-beta spine of amyloid-like fibrils. Nature 435:773–778

    Article  CAS  PubMed  Google Scholar 

  48. Ollague W, Ollague J, Ferretti H (1990) Epidemiology of primary cutaneous amyloidoses in South America. Clin Dermatol 8:25–29

    Article  CAS  PubMed  Google Scholar 

  49. Pandhi R, Kaur I, Kumar B (2002) Lack of effect of dimethylsulphoxide in cutaneous amyloidosis. J Dermatolog Treat 13:11–14

    Article  CAS  PubMed  Google Scholar 

  50. Park J, Kahng B, Hwang W (2009) Thermodynamic selection of steric zipper patterns in the amyloid cross-beta spine. PLoS Comput Biol 5:e1000492

    Article  PubMed  Google Scholar 

  51. Powell AM, Albert S, Bhogal B, Black MM (2005) Discoid lupus erythematosus with secondary amyloidosis. Br J Dermatol 153:746–749

    Article  CAS  PubMed  Google Scholar 

  52. Raap U, Kapp A, Wedi B, Stander S (2010) Pruritus and urticaria. Hautarzt 61:737–742

    Article  CAS  PubMed  Google Scholar 

  53. Ramsook CB, Tan C, Garcia MC et al (2010) Yeast cell adhesion molecules have functional amyloid-forming sequences. Eukaryot Cell 9:393–404

    Article  CAS  PubMed  Google Scholar 

  54. Rubinow A, Cohen AS (1981) Skin involvement in familial amyloidotic polyneuropathy. Neurology 31:1341–1345

    CAS  PubMed  Google Scholar 

  55. Ruzicka T, Donhauser G, Linke RP et al (1990) Cutaneous amyloidoses. Hautarzt 41:245–255

    CAS  PubMed  Google Scholar 

  56. Sawaya MR, Sambashivan S, Nelson R et al (2007) Atomic structures of amyloid cross-beta spines reveal varied steric zippers. Nature 447:453–457

    Article  CAS  PubMed  Google Scholar 

  57. Schreml S, Kaiser E, Szeimies RM et al (2010) Amyloid in skin and brain: what’s the link? Exp Dermatol [Epub ahead of print]

  58. Schreml S, Szeimies RM, Vogt T et al (2010) Cutaneous amyloidoses and systemic amyloidoses with cutaneous involvement. Eur J Dermatol 20:152–160

    PubMed  Google Scholar 

  59. Shirahama T, Cohen AS (1965) Structure of amyloid fibrils after negative staining and high-resolution electron microscopy. Nature 206:737–738

    Article  CAS  PubMed  Google Scholar 

  60. Sidwell RU, Francis N, Roberts NM, Staughton RC (2002) Allotropic cutaneous amyloidosis: coincidence or progression? Clin Exp Dermatol 27:526–528

    Article  CAS  PubMed  Google Scholar 

  61. Tan T (1990) Epidemiology of primary cutaneous amyloidoses in southeast Asia. Clin Dermatol 8:20–24

    Article  CAS  PubMed  Google Scholar 

  62. Truhan AP, Garden JM, Roenigk HH Jr (1986) Nodular primary localized cutaneous amyloidosis: immunohistochemical evaluation and treatment with the carbon dioxide laser. J Am Acad Dermatol 14:1058–1062

    Article  CAS  PubMed  Google Scholar 

  63. Vestey JP, Tidman MJ, McLaren KM (1994) Primary nodular cutaneous amyloidosis – long-term follow-up and treatment. Clin Exp Dermatol 19:159–162

    Article  CAS  PubMed  Google Scholar 

  64. Virchow R (1854) Zur Cellulose-Frage. Virchows Archiv Pathol Anat Physiol Klin Med 8:416–426

    Article  Google Scholar 

  65. von Rokitansky C (1842) Handbuch der pathologischen Anatomie. 3:311

  66. Wall JS, Gupta V, Wilkerson M et al (2004) Structural basis of light chain amyloidogenicity: comparison of the thermodynamic properties, fibrillogenic potential and tertiary structural features of four Vlambda6 proteins. J Mol Recognit 17:323–331

    Article  CAS  PubMed  Google Scholar 

  67. Wang WJ, Lin CS, Wong CK (1986) Response of systemic amyloidosis to dimethyl sulfoxide. J Am Acad Dermatol 15:402–405

    Article  CAS  PubMed  Google Scholar 

  68. Wang X, Zhou Y, Ren JJ et al (2010) Gatekeeper residues in the major curlin subunit modulate bacterial amyloid fiber biogenesis. Proc Natl Acad Sci U S A 107:163–168

    Article  CAS  PubMed  Google Scholar 

  69. Westermark P, Davey E, Lindbom K, Enqvist S (2006) Subcutaneous fat tissue for diagnosis and studies of systemic amyloidosis. Acta Histochem 108:209–213

    Article  PubMed  Google Scholar 

  70. Zhang Q, Putheti P, Zhou Q et al (2008) Structures and biological functions of IL-31 and IL-31 receptors. Cytokine Growth Factor Rev 19:347–356

    Article  PubMed  Google Scholar 

  71. Zhang Z, Chen H, Lai L (2007) Identification of amyloid fibril-forming segments based on structure and residue-based statistical potential. Bioinformatics 23:2218–2225

    Article  CAS  PubMed  Google Scholar 

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  1. Klinik und Poliklinik für Dermatologie, Universitätsklinikum Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Deutschland

    S. Schreml, M. Landthaler & P. Babilas

  2. Klinik für Dermatologie und Allergologie, Klinikum Vest GmbH, Recklinghausen, Deutschland

    R.-M. Szeimies

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  1. S. Schreml
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Schreml, S., Szeimies, RM., Landthaler, M. et al. Kutane Amyloidosen. Hautarzt 62, 55–62 (2011). https://doi.org/10.1007/s00105-010-2073-x

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