Xanthome

Gelbknötchen

Hautveränderungen, welche durch Einlagerung in Serumlipoproteinen in Makrophagen entstehen. Diese können sowohl bei Hyperlipidämie (als erste klinische Zeichen) als auch bei Normolipidämie auftreten.

Xanthelasmen sind flache Xanthome der Augenlider, obschon sie strikte gesehen eine eigene Entität darstellen.

Sowohl eine quantitative Erhöhung von Serumlipiden, als auch ein gestörter Abbau von Lipoproteinen können ursächlich sein.

• Gelb/rötlich/bräunliche, eher scharf begrenzte Makulae, Papeln oder Knoten.
  • Eruptive Xanthome
    • Klinik
      • Bilden sich relativ schnell (Tage - Wochen)
      • Können disseminiert auftreten
    • Lokalisation
      • Gluteal, Extremitätenstreckseiten
    • Assoziationen
      • Erhöhung von triglyzeridreichen Lipoproteinen (Chylomikronen, VLDL)
      • Diabetes mellitus
  • Tuberöse Xanthome
    • Klinik
      • Flächig ausgedehnte gelbliche, oft symmetrische Plaques oder Knoten
    • Lokalisation
      • Knien, Händen, Füßen und Achillessehnen
    • Assoziation
      • Familiärer Dysbetalipoproteinämie,
      • Heterozygoter familiärer Hypercholesterinämie
      • Familiärem Apolipoprotein-B-100-Defekt
  • Sehnenxanthome
    • Lokalisation
      • Insbesondere an Strecksehnen (Finger), Ellenbögen, Patellarsehnen und Achillessehne.
    • Assoziation
      • Familiäre Hypercholesterinämie
      • Familiäre Apolipoprotein-B-100-Defekt
      • Phytosterolämie
    • Differentialdiagnose
      • Gichttophi
      • Rheumaknoten
    • Therapie
      • Senkung von LDL-Cholesterin
  • Plane Xanthome
    • Klinik
      • Flächenhafte, gelbliche Hautläsionen
    • Assoziation
      • z.B. bei homozygoter, familiärer Hypercholesterinämie
  • Xanthoma verruciforme
    • Klinik
      • Warzenartige kutane und muköse Veränderungen.
    • Differentialdiagnose
    • Verruca vulgaris
    • Filiformen Warze
      • Eine Unterscheidung ist nur anhand der Histopathologie möglich

Xanthelasmen

• Xanthelasma palpebrarum:
  Ätiopathogenese
  • 50% aller Patienten mit Xanthelasmen leiden an einer Dysfunktion des Lipoproteinstoffwechsels.
• Lokalisation
  • Ober- und Unterlider medial
• Klinik
  • siehe oben
  • Sonderformen:
    • Xanthelasma cysticum
      • Bei komedoartige Hyperkeratosen sowie milienartigen Zysten, welche in einem Xanthelasma zu finden sind, spricht man von einem Xanthelasma cysticum
      • Hyperpigmentierungen der Augenlider
      • Differenzialdiagnostisch
        • Hidradenome (Syringome)
        • Milien
        • Solare Elastose mit Zysten und Komedonen
      • Prognose
        • Langsame Progredienz, trotz Therapie
  • Bei frühzeitigem Auftreten fungieren Xanthelasmen als Indikator atherogener Dyslipoproteinämie
  • Hutchinson-Syndrom
    • Weist auf Leberstoffwechselstörungen hin

• Anamnese
• Klinik
• Ggf. Biopsie
• Blutfettwerte (nüchtern)

Können fast überall vorkommen, vor allem Rumpf, Streckseiten, Glutalregion, über Sehnen, interdigital.

• Schaumzellen (lipidspeichernde Makrophagen), manchmal Touton'sche-Riesenzellen (wenn zahlreich, charakteristisch für JXG).
• Fibrosierung und Cholesteringranulome im Verlauf.

1. Xanthoma disseminatum, in SpringerReference. Springer Science + Business Media.
2. Pseudoxanthoma elasticum, in SpringerReference. Springer Science + Business Media.
3. Exogenous pseudoxanthoma elasticum: a new case in an old farmer. Acta Dermato-Venereologica, 1998. 78(2): p. 153-154.
4. Homozygous familial hypercholesterolemia presenting as linear intertriginous xanthomas. Journal of the American Academy of Dermatology, 2012. 66(4): p. AB130.
5. Adamson, H.G., A NOTE ON MULTIPLE ERUPTIVE XANTHOMA IN INFANTS: NAEVO-XANTHO-ENDOTHELIOMA (McDONAGH). Br J Dermatol, 1936. 48(7): p. 366-370.
6. Aessopos, A., Elastic tissue abnormalities resembling pseudoxanthoma elasticum in beta thalassemia and the sickling syndromes. Blood, 2002. 99(1): p. 30-35.
7. Alam, M., et al., Tuberous Xanthomas in Sitosterolemia. Pediatric Dermatology, 2000. 17(6): p. 447-449.
8. Altman, J., Xanthoma Disseminatum. Arch Dermatol, 1962. 86(5): p. 582.
9. Baron, J., J.R. Barrie, and G.S. Raymond, Xanthoma Disseminatum: A Rare Cause of Upper Airway Narrowing. American Journal of Roentgenology, 2003. 180(4): p. 1180-1181.
10. Bel, S., et al., Cerebrotendinous xanthomatosis. Journal of the American Academy of Dermatology, 2001. 45(2): p. 292-295.
11. Blobstein, S.H., Bone Lesions in Xanthoma Disseminatum. Arch Dermatol, 1985. 121(10): p. 1313.
12. Bolognia, J.L. and I. Braverman, Pseudoxanthoma-elasticum-Like Skin Changes Induced by Penicillamine. Dermatology, 1992. 184(1): p. 12-18.
13. Bormate, A.B., P.E. Leboit, and T.H. McCalmont, Perifollicular Xanthomatosis as the Hallmark of Axillary Fox-Fordyce Disease. Arch Dermatol, 2008. 144(8).
14. Breier, F., et al., Papular xanthoma: a clinicopathological study of 10 cases. J Cutan Pathol, 2002. 29(4): p. 200-206.
15. Broeshart, J.H., et al., Normolipemic plane xanthoma associated with adenocarcinoma and severe itch. Journal of the American Academy of Dermatology, 2003. 49(1): p. 119-122.
16. Bude, R.O., R.S. Adler, and D.R. Bassett, Diagnosis of Achilles tendon xanthoma in patients with heterozygous familial hypercholesterolemia: MR vs sonography. American Journal of Roentgenology, 1994. 162(4): p. 913-917.
17. Buka, R., et al., Pseudoxanthoma elasticum and calcinosis cutis. Journal of the American Academy of Dermatology, 2000. 43(2): p. 312-315.
18. Bundino, S., A.M. Zina, and F. Aloi, Papular Xanthoma. Dermatology, 1988. 177(6): p. 382-385.
19. Caputo, R., E. Passoni, and S. Cavicchini, Papular Xanthoma Associated with Angiokeratoma of Fordyce: Considerations on the Nosography of This Rare Non-Langerhans Cell Histiocytoxanthomatosis. Dermatology, 2003. 206(2): p. 165-168.
20. Caputo, R., et al., The Various Clinical Patterns of Xanthoma disseminatum. Dermatology, 1995. 190(1): p. 19-24.
21. Carpo, B.G., et al., Treatment of Cutaneous Lesions of Xanthoma Disseminatum with a CO2 Laser. Dermatologic Surgery, 1999. 25(10): p. 751-754.
22. Chang, H.Y., et al., Eruptive Xanthomas Associated With Olanzapine Use. Arch Dermatol, 2003. 139(8).
23. Choi, G.S., et al., Osteoma cutis coexisting with cutis laxa-like pseudoxanthoma elasticum. Journal of the American Academy of Dermatology, 2000. 43(2): p. 337-339.
24. Cruz, P.D., C. East, and P.R. Bergstresser, Dermal, subcutaneous, and tendon xanthomas: Diagnostic markers for specific lipoprotein disorders. Journal of the American Academy of Dermatology, 1988. 19(1): p. 95-111.
25. Dilek, F.H., et al., Atypical fibroxanthoma of the skin and the lower lip in xeroderma pigmentosum. Br J Dermatol, 2000. 143(3): p. 618-620.
26. Fretzin, D.F. and E.B. Helwig, Atypical fibroxanthoma of the skin. A clinicopathologic study of 140 cases. Cancer, 1973. 31(6): p. 1541-1552.
27. Goldstein, G.D., The Koebner response with eruptive xanthomas. Journal of the American Academy of Dermatology, 1984. 10(6): p. 1064-1065.
28. GrÖNblad, E., ANGIOID STREAKS - PSEUDOXANTHOMA ELASTICUM. Acta Ophthalmologica, 1929. 7(1-4): p. 329-329.
29. Hendig, D., Role of Serum Fetuin-A, a Major Inhibitor of Systemic Calcification, in Pseudoxanthoma Elasticum. Clinical Chemistry, 2005. 52(2): p. 227-234.
30. Hentzer, B., et al., In vitro calcification of connective tissue from uninvolved skin of patients with pseudoxanthoma elasticum. Archives for Dermatological Research, 1977. 258(2): p. 219-222.
31. Hirata, Y., et al., Low density lipoprotein oxidized in xanthoma tissue induces the formation and infiltration of foam cells. Journal of Dermatological Science, 2002. 30(3): p. 248-255.
32. Hu, X., et al., ABCC6/MRP6 mutations: further insight into the molecular pathology of pseudoxanthoma elasticum. Eur J Hum Genet, 2003. 11(3): p. 215-224.
33. Jaber, P.W., et al., Eruptive xanthomas during pregnancy. Journal of the American Academy of Dermatology, 1992. 27(2): p. 300-302.
34. Jain, R., et al., Diffuse Cutaneous Mastocytosis: Pseudoxanthomatous Variant. The Journal of Dermatology, 2002. 29(6): p. 354-356.
35. Kajinami, K., et al., Long-term probucol treatment results in regression of xanthomas, but in progression of coronary atherosclerosis in a heterozygous patient with familial hypercholesterolemia. Atherosclerosis, 1996. 120(1-2): p. 181-187.
36. Khan, Z.M. and C.J. Cockerell, Atypical Fibroxanthoma with Osteoclast-Like Multinucleated Giant Cells. The American Journal of Dermatopathology, 1997. 19(2): p. 174-179.
37. Khandpur, S., et al., Rare association of xanthoma disseminatum with skeletal involvement. Australas J Dermatol, 2003. 44(3): p. 190-193.
38. LaRusso, J., et al., Elevated Dietary Magnesium Prevents Connective Tissue Mineralization in a Mouse Model of Pseudoxanthoma Elasticum (Abcc6−/−). Journal of Investigative Dermatology, 2009. 129(6): p. 1388-1394.
39. Lebwohl, M., et al., Diagnosis of Pseudoxanthoma Elasticum by Scar Biopsy in Patients without Characteristic Skin Lesions. New England Journal of Medicine, 1987. 317(6): p. 347-350.
40. Leitersdorf, E., et al., Frameshift and splice-junction mutations in the sterol 27-hydroxylase gene cause cerebrotendinous xanthomatosis in Jews or Moroccan origin. Journal of Clinical Investigation, 1993. 91(6): p. 2488-2496.
41. Li, Q., et al., Mutations in the GGCX and ABCC6 Genes in a Family with Pseudoxanthoma Elasticum-Like Phenotypes. Journal of Investigative Dermatology, 2009. 129(3): p. 553-563.
42. Mainetti, C., I. Masouyé, and J.H. Saurat, Pseudoxanthoma elasticiun-like lesions in the L-tryptophan-induced eosinophilia-myalgia syndrome. Journal of the American Academy of Dermatology, 1991. 24(4): p. 657-658.
43. Mehra, S., et al., A Novel Somatic Mutation of the 3β-Hydroxysteroid Dehydrogenase Gene in Sporadic Cutaneous Verruciform Xanthoma. Arch Dermatol, 2005. 141(10).
44. Mirza, B. and D. Weedon, Atypical fibroxanthoma: A clinicopathological study of 89 cases. Australas J Dermatol, 2005. 46(4): p. 235-238.
45. Mo, H.J., et al., Two Cases of Type V Hyperlipoproteinemia and Eruptive Xanthomas associated with Diabetes Mellitus. Annals of Dermatology, 2001. 13(3): p. 175.
46. Montgomery, H., XANTHOMATOSIS. Archives of Dermatology and Syphilology, 1938. 37(3): p. 373.
47. Neil, H.A.W., et al., Comparison of the risk of fatal coronary heart disease in treated xanthomatous and non-xanthomatous heterozygous familial hypercholesterolaemia: a prospective registry study. Atherosclerosis, 2003. 170(1): p. 73-78.
48. Neldner, K.H., Pseudoxanthoma Elasticum. International Journal of Dermatology, 1988. 27(2): p. 98-100.
49. Nickoloff, B.J., Perforating Pseudoxanthoma Elasticum Associated With Chronic Renal Failure and Hemodialysis. Arch Dermatol, 1985. 121(10): p. 1321.
50. Oosterveer, D.M., et al., Differences in characteristics and risk of cardiovascular disease in familial hypercholesterolemia patients with and without tendon xanthomas: A systematic review and meta-analysis. Atherosclerosis, 2009. 207(2): p. 311-317.
51. Parker, F., Xanthomas and hyperlipidemias. Journal of the American Academy of Dermatology, 1985. 13(1): p. 1-30.
52. Parker, F., Normocholesterolemic Xanthomatosis. Arch Dermatol, 1986. 122(11): p. 1253.
53. Pfeiffer, G., et al., Cerebrocutaneous Xanthoma disseminatum and Disseminated Demyelinating Encephalomyelitis. European Neurology, 2000. 44(2): p. 123-124.
54. Quaglino, P., et al., Immunohistologic Findings and Adhesion Molecule Pattern in Primary Pure Cutaneous Rosai-Dorfman Disease With Xanthomatous Features. The American Journal of Dermatopathology, 1998. 20(4): p. 393-398.
55. Repiso, T., et al., Generalized eruptive histiocytoma evolving into xanthoma disseminatum in a 4-year-old boy. British Journal of Dermatology, 2010. 132(6): p. 978-982.
56. Ringpfeil, F., et al., Pseudoxanthoma elasticum: Mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter. Proceedings of the National Academy of Sciences, 2000. 97(11): p. 6001-6006.
57. Ringpfeil, F., et al., Pseudoxanthoma Elasticum Is a Recessive Disease Characterized by Compound Heterozygosity. Journal of Investigative Dermatology, 2006. 126(4): p. 782-786.
58. Rowland, R.S., XANTHOMATOSIS AND THE RETICULOENDOTHELIAL SYSTEM. Arch Intern Med (Chic), 1928. 42(5): p. 611.
59. Rupec, R.A. and M. Schaller, Xanthoma disseminatum. International Journal of Dermatology, 2002. 41(12): p. 911-913.
60. Sanchez, R.L., Papular Xanthoma. Arch Dermatol, 1985. 121(5): p. 626.
61. Seaton, E.D., G.J. Pillai, and A.C. Chu, Treatment of xanthoma disseminatum with cyclophosphamide. Br J Dermatol, 2004. 150(2): p. 346-349.
62. Sperhake, J.P. and J. Matschke, Zerebrotendin�se Xanthomatose?eine behandelbare Stoffwechselerkrankung. Der Nervenarzt, 2004. 75(6).
63. Uitto, J. and Q. Jiang, Pseudoxanthoma Elasticum-Like Phenotypes: More Diseases than One. Journal of Investigative Dermatology, 2007. 127(3): p. 507-510.
64. Uitto, J., Q. Li, and Q. Jiang, Pseudoxanthoma Elasticum: Molecular Genetics and Putative Pathomechanisms. Journal of Investigative Dermatology, 2010. 130(3): p. 661-670.
65. Vanakker, O.M., et al., Pseudoxanthoma Elasticum-Like Phenotype with Cutis Laxa and Multiple Coagulation Factor Deficiency Represents a Separate Genetic Entity. Journal of Investigative Dermatology, 2007. 127(3): p. 581-587.
66. Viljoen, D.L., C. Bloch, and P. Beighton, Plastic Surgery in Pseudoxanthoma Elasticum. Plastic and Reconstructive Surgery, 1990. 85(2): p. 233-238.
67. Weber, F.P., A REMARKABLE CASE OF XANTHOMA TUBEROSUM MULTIPLEX. Br J Dermatol, 1917. 29(3): p. 202-209.
68. Yamamoto, A., et al., Effects of probucol on xanthomata regression in familial hypercholesterolemia. The American Journal of Cardiology, 1986. 57(16): p. H29-H35.
69. Zahorcsek, Z.f., I. Schneider, and J. Hortob�gyi, Erfolgreiche Behandlung einer eruptiven Xanthomatose mit Acipimox. Der Hautarzt, 1995. 46(2): p. 124-126.
70. Zelger, B., Histologic and Immunohistochemical Study Comparing Xanthoma Disseminatum and Histiocytosis X. Arch Dermatol, 1992. 128(9): p. 1207.
71. Lebwohl, Mark. Treatment of Skin Disease: Comprehensive Therapeutic Strategies. Elsevier, 2014. Print.