Xanthoma

Last Updated: 2020-11-23

Author(s): -

Skin changes caused by deposition in serum lipoproteins in macrophages. These occur in both hyperlipidemia (as first clinical signs) and normolipidemia.

Xanthelasma are flat xanthomas of the eyelids, although strictly speaking they are a separate entity.

Both a quantitative increase of serum lipids and a disturbed degradation of lipoproteins can be the cause.

  • Yellow / reddish / brownish, rather sharply defined macules, papules or nodules.

 

Eruptive xanthomas

  • Clinical features
    • Forming relatively fast (days to weeks)

    • Can occur disseminated

  • Localization
    • Gluteal, the extension sides of the extremities

  • Associations
    • ↑ Triglyceride-rich lipoproteins (chylomicrons, VLDL)

    • Diabetes mellitus

 

Tuberous xanthomas

  • Clinical features
    • Yellowish, often symmetrical plaques or nodules extending over a large area

  • Localization
    • Knees, hands, feet and Achilles tendons

  • Association
    • Familial dysbetalipoproteinemia,
    • Heterozygous familial hypercholesterolemia

    • Familial apolipoprotein B-100 defect.

 

Tendon xanthomas

  • Localization
    • Especially on extensor tendons (fingers), elbows, patellar tendons and Achilles tendon.

  • Association
    • Familial hypercholesterolemia

    • Familial apolipoprotein B-100 defect

    • Phytosterolemia
  • Differential diagnosis

    • Gouty Tophi
    • Rheumatoid nodules
  • Therapy

    • Lowering LDL cholesterol

 

Plan xanthomas

  • Clinical features
    • Large, yellowish skin lesions.

  • Association
    • For example, in homozygous familial hypercholesterolemia

  • Xanthoma verruciforme
    • Clinical features
      • Wart-like cutaneous and mucous changes.

    • Differential diagnosis

      • Verruca vulgaris
      • Filiform wart
        • A distinction is only possible on the basis of histopathology.

 

Xanthelasmata

  • Xanthelasma palpebrarum:
    Etiopathogenesis
    • 50% of all patients with xanthelasma suffer from dysfunction of lipoprotein metabolism.

  • Localization
    •  Upper and lower medial eyelids

  • Clinical features
    • S.o
    • Special forms::
      • Xanthelasma cysticum
        • In cases of comedo-like hyperkeratoses as well as miliary cysts which are found in a Xanthelasma, one speaks of a Xanthelasma cysticum.

        • Hyperpigmentation of the eyelids

  • Differential diagnosis
    • Hidradenoma (syringoma)

    • Milia
    • Solar elastosis with cysts and comedones

  • Prognosis
    • Slow progression despite therapy

      • In the case of premature occurrence, xanthelasmas act as an indicator of atherogenic Dyslipoproteinemia

      • Hutchinson's syndrome
        • Indicates liver metabolism disorders.

  • Medical history
  • Clinical features
  • Biopsy (if necessary)
  • Blood lipid levels

Can occur almost everywhere, especially trunk, extensor sides, glutal region, over tendons, interdigital.

  • Foam cells (lipid-storing macrophages), sometimes Touton giant cells (if numerous, characteristic of JXG).
  • In the course fibrosis and cholesterol granulomas.

 

Therapy of 1st choice by Lebwohl Evidence level

Low-fat diet and lipid-lowering therapy

B
   
Therapy of the 2nd choice by Lebwohl  
Surgical excision B
CO2 Laser B
Erbium: YAG laser C
Pulsed dye laser B
Argon laser B
Q-switched Nd: YAG laser D
KTP laser D
1450 nm diode laser D
Low-voltage radiofrequency C
   

Therapy of the 3rd choice by Lebwohl

 
Di-or-trichloracetic acid C
Cryotherapy E
Bleomycin B

Triamcinolone (intralesional)

D
Chlorambucil E
Prednisolone E
Intravenous immunoglobulins  E

 

  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, Zerebrotendinse 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.