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Current Dermatology Reports

, Volume 7, Issue 3, pp 125–135 | Cite as

Livedoid Vasculopathy: an Updated Review

  • Robert Micieli
  • Afsaneh Alavi
Wound Care and Healing (H Lev-Tov, Section Editor)
  • 48 Downloads
Part of the following topical collections:
  1. Topical Collection on Wound Care and Healing

Abstract

Purpose of Review

To highlight the most recent findings in the literature on livedoid vasculopathy while providing a basic review of the disease.

Recent Findings

Lipoprotein(a) and plasminogen activator inhibitor continue to develop evidence supporting their involvement in the pathogenesis of livedoid vasculopathy. Systematic review of the literature has revealed that anticoagulants are the most commonly reported treatments in case series followed by anabolic steroids, antiplatelets, and intravenous immunoglobulins. No randomized or controlled trials have been performed studying treatment efficacy.

Summary

The literature continues to support the hypothesis that livedoid vasculopathy is a disease of hypercoagulability and impaired fibrinolysis. There is no established treatment for livedoid vasculopathy, although a wide variety of treatments have been used to achieve partial or complete remission. Anticoagulants continue to be the most commonly reported treatment in the literature with rivaroxaban used most frequently.

Keywords

Livedoid Vasculopathy Atrophie Blanche Treatment 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Jockenhofer F, Chapot V, Stoffels-Weindorf M, et al. Bacterial spectrum colonizing chronic leg ulcers: a 10-year comparison from a German wound care center. J Dtsch Dermatol Ges. 2014;12(12):1121–7.PubMedGoogle Scholar
  2. 2.
    Jorizzo JL. Livedoid vasculopathy: what is it? Arch Dermatol. 1998;134(4):491–3.PubMedCrossRefGoogle Scholar
  3. 3.
    Hairston BR, Davis MD, Pittelkow MR, Ahmed I. Livedoid vasculopathy: further evidence for procoagulant pathogenesis. Arch Dermatol. 2006;142(11):1413–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Criado PR, Rivitti EA, Sotto MN, de Carvalho JF. Livedoid vasculopathy as a coagulation disorder. Autoimmun Rev. 2011;10(6):353–60.PubMedCrossRefGoogle Scholar
  5. 5.
    Alavi A, Hafner J, Dutz JP, Mayer D, Sibbald RG, Criado PR, et al. Livedoid vasculopathy: an in-depth analysis using a modified Delphi approach. J Am Acad Dermatol. 2013;69(6):1033–1042 e1031.PubMedCrossRefGoogle Scholar
  6. 6.
    Renner R, Dissemond J, Goerge T, Hoff N, Kroger K, Erfurt-Berge C. Analysis of the German DRG data for livedoid vasculopathy and calciphylaxis. J Eur Acad Dermatol Venereol. 2017;31(11):1884–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Winkelmann RK, Schroeter AL, Kierland RR, Ryan TM. Clinical studies of livedoid vasculitis: (segmental hyalinizing vasculitis). Mayo Clin Proc. 1974;49(10):746–50.PubMedGoogle Scholar
  8. 8.
    Di Giacomo TB, Hussein TP, Souza DG, Criado PR. Frequency of thrombophilia determinant factors in patients with livedoid vasculopathy and treatment with anticoagulant drugs—a prospective study. J Eur Acad Dermatol Venereol. 2010;24(11):1340–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Polo Gascon MR, de Carvalho JF, de Souza Espinel DP, Barros AM, Alavi A, Criado PR. Quality-of-life impairment in patients with livedoid vasculopathy. J Am Acad Dermatol. 2014;71(5):1024–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Hong J, Koo B, Koo J. The psychosocial and occupational impact of chronic skin disease. Dermatol Ther. 2008;21(1):54–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Vaughan DE. PAI-1 and atherothrombosis. J Thromb Haemost. 2005;3(8):1879–83.CrossRefPubMedGoogle Scholar
  12. 12.
    Agirbasli M. Pivotal role of plasminogen-activator inhibitor 1 in vascular disease. Int J Clin Pract. 2005;59(1):102–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Khenifer S, Thomas L, Balme B, Dalle S. Livedoid vasculiltis associated with a double heterozygous factor V Leiden and prothrombin G20210A gene mutations. Clin Exp Dermatol. 2009;34(8):e811–3.PubMedCrossRefGoogle Scholar
  14. 14.
    Davis MD, Wysokinski WE. Ulcerations caused by livedoid vasculopathy associated with a prothrombotic state: response to warfarin. J Am Acad Dermatol. 2008;58(3):512–5.PubMedCrossRefGoogle Scholar
  15. 15.
    Irani-Hakime NA, Stephan F, Kreidy R, Jureidini I, Almawi WY. Livedoid vasculopathy associated with combined prothrombin G20210A and factor V (Leiden) heterozygosity and MTHFR C677T homozygosity. J Thromb Thrombolysis. 2008;26(1):31–4.PubMedCrossRefGoogle Scholar
  16. 16.
    Criado PR, Alavi A, Kirsner RS. Elevated levels of coagulation factor VIII in patients with venous leg ulcers. Int J Low Extrem Wounds. 2014;13(2):130–4.PubMedCrossRefGoogle Scholar
  17. 17.
    Calamia KT, Balabanova M, Perniciaro C, Walsh JS. Livedo (livedoid) vasculitis and the factor V Leiden mutation: additional evidence for abnormal coagulation. J Am Acad Dermatol. 2002;46(1):133–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Cocuroccia B, Tonanzi T, Menaguale G, Fazio M, Girolomoni G. Livedoid vasculopathy and skin ulcers in patients with inherited thrombophilia. Eur J Dermatol. 2002;12(4):360–3.PubMedGoogle Scholar
  19. 19.
    Hairston BR, Davis MD, Gibson LE, Drage LA. Treatment of livedoid vasculopathy with low-molecular-weight heparin: report of 2 cases. Arch Dermatol. 2003;139(8):987–90.PubMedCrossRefGoogle Scholar
  20. 20.
    Yong AA, Tan AW, Giam YC, Tang MB. Livedoid vasculopathy and its association with factor V Leiden mutation. Singap Med J. 2012;53(12):e258–60.Google Scholar
  21. 21.
    Kavala M, Kocaturk E, Zindanci I, Turkoglu Z, Altintas S. A case of livedoid vasculopathy associated with factor V Leiden mutation: successful treatment with oral warfarin. J Dermatol Treat. 2008;19(2):121–3.CrossRefGoogle Scholar
  22. 22.
    Hurabielle C, Sebille G, Barrou B, Moguelet P, Frances C, Barete S. Livedoid vasculopathy associated with HIV infection in two patients: a causal relationship? Acta Derm Venereol. 2016;96(6):844–5.PubMedGoogle Scholar
  23. 23.
    • Weishaupt C, Strolin A, Kahle B, et al. Anticoagulation with rivaroxaban for livedoid vasculopathy (RILIVA): a multicentre, single-arm, open-label, phase 2a, proof-of-concept trial. Lancet Haematol. 2016;3(2):e72–9. One of the largest case series studying rivaroxaban efficacy in livedoid vasculopathy. Found improvement in pain, ulceration, and quality of life with minimal side effects with rivaroxaban. PubMedCrossRefGoogle Scholar
  24. 24.
    Frances C, Barete S. Difficult management of livedoid vasculopathy. Arch Dermatol. 2004;140(8):1011.PubMedCrossRefGoogle Scholar
  25. 25.
    Monshi B, Posch C, Vujic I, Sesti A, Sobotka S, Rappersberger K. Efficacy of intravenous immunoglobulins in livedoid vasculopathy: long-term follow-up of 11 patients. J Am Acad Dermatol. 2014;71(4):738–44.PubMedCrossRefGoogle Scholar
  26. 26.
    Meiss F, Marsch WC, Fischer M. Livedoid vasculopathy. The role of hyperhomocysteinemia and its simple therapeutic consequences. Eur J Dermatol. 2006;16(2):159–62.PubMedGoogle Scholar
  27. 27.
    Errichetti E, Stinco G. Recalcitrant livedoid vasculopathy associated with hyperhomocysteinaemia responding to folic acid and vitamins B6/B12 supplementation. Acta Derm Venereol. 2016;96(7):987–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Rampf J, Sunderkotter C, Hirschfeld G, Scharffetter-Kochanek K, Weiss JM. Methylenetetrahydrofolate reductase polymorphism associated with moderate hyperhomocysteinaemia in a patient with livedo vasculopathy: treatment with vitamin supplementation and low molecular weight heparin. Br J Dermatol. 2006;155(4):850–2.PubMedCrossRefGoogle Scholar
  29. 29.
    Shankar S, Vasudevan B, Deb P, Langer V, Verma R, Nair V. Livedoid vasculopathy—a vasculitic mimic. Arthritis Rheum. 2013;65(3):791.PubMedCrossRefGoogle Scholar
  30. 30.
    Browning CE, Callen JP. Warfarin therapy for livedoid vasculopathy associated with cryofibrinogenemia and hyperhomocysteinemia. Arch Dermatol. 2006;142(1):75–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Kishibe M, Komatsu S, Ishida-Yamamoto A, Iizuka H. Livedo vasculopathy associated with methylenetetrahydrofolate reductase C677T homozygosity. J Dermatol. 2012;39(1):91–4.PubMedCrossRefGoogle Scholar
  32. 32.
    Cardoso R, Goncalo M, Tellechea O, et al. Livedoid vasculopathy and hypercoagulability in a patient with primary Sjogren’s syndrome. Int J Dermatol. 2007;46(4):431–4.PubMedCrossRefGoogle Scholar
  33. 33.
    Abou Rahal J, Ishak RS, Otrock ZK, Kibbi AG, Taher AT. Livedoid vasculopathy in a patient with lupus anticoagulant and MTHFR mutation: treatment with low-molecular-weight heparin. J Thromb Thrombolysis. 2012;34(4):541–4.PubMedCrossRefGoogle Scholar
  34. 34.
    Mirrakhimov AE, Velasquez Kho E, Ali A. Painless livedoid vasculopathy in a patient with G20210A prothrombin gene mutation. Case Rep Med. 2012;2012:910231.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Gotlib J, Kohler S, Reicherter P, Oro AE, Zehnder JL. Heterozygous prothrombin G20210A gene mutation in a patient with livedoid vasculitis. Arch Dermatol. 2003;139(8):1081–3.PubMedCrossRefGoogle Scholar
  36. 36.
    Anavekar NS, Kelly R. Heterozygous prothrombin gene mutation associated with livedoid vasculopathy. Aust J Dermatol. 2007;48(2):120–3.CrossRefGoogle Scholar
  37. 37.
    Antunes J, Filipe P, Andre M, Fraga A, Miltenyi G, Marques Gomes M. Livedoid vasculopathy associated with plasminogen activator inhibitor-1 promoter homozygosity (4G/4G) and prothrombin G20210A heterozygosity: response to t-PA therapy. Acta Derm Venereol. 2010;90(1):91–2.PubMedCrossRefGoogle Scholar
  38. 38.
    Drucker CR, Duncan WC. Antiplatelet therapy in atrophie blanche and livedo vasculitis. J Am Acad Dermatol. 1982;7(3):359–63.PubMedCrossRefGoogle Scholar
  39. 39.
    Kawakami T, Kawasaki K, Mizoguchi M, Soma Y. Therapeutic effect of lipoprostaglandin E1 on livedoid vasculitis associated with essential cryoglobulinaemia. Br J Dermatol. 2007;157(5):1051–3.PubMedCrossRefGoogle Scholar
  40. 40.
    Nikolova K, Popov J, Obreshkova E. Leg ulcerations due to livedo vasculitis: successful combined therapy with pentoxifylline and nifedipine. J Eur Acad Dermatol Venereol. 1995;5:54–8.CrossRefGoogle Scholar
  41. 41.
    Kuno Y, Numata T, Tsuji T. Livedo vasculitis associated with regional cytophagic histiocytoses. J Dermatol. 1999;26(12):817–20.PubMedCrossRefGoogle Scholar
  42. 42.
    Verma R, Hadid TH, Dhamija R, Moad JC, Loehrke ME. Livedoid vasculopathy in a woman with multiple myeloma. South Med J. 2010;103(8):848–9.PubMedCrossRefGoogle Scholar
  43. 43.
    Juan WH, Chan YS, Lee JC, Yang LC, Hong HS, Yang CH. Livedoid vasculopathy: long-term follow-up results following hyperbaric oxygen therapy. Br J Dermatol. 2006;154(2):251–5.PubMedCrossRefGoogle Scholar
  44. 44.
    Tuchinda P, Tammaro A, Gaspari AA. Successful long-term use of intravenous immunoglobulin to treat livedoid vasculopathy associated with plasminogen activator inhibitor-1 promoter homozygosity. Arch Dermatol. 2011;147(10):1224–5.PubMedCrossRefGoogle Scholar
  45. 45.
    Deng A, Gocke CD, Hess J, Heyman M, Paltiel M, Gaspari A. Livedoid vasculopathy associated with plasminogen activator inhibitor-1 promoter homozygosity (4G/4G) treated successfully with tissue plasminogen activator. Arch Dermatol. 2006;142(11):1466–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Castillo-Martinez C, Moncada B, Valdes-Rodriguez R, Gonzalez FJ. Livedoid vasculopathy (LV) associated with sticky platelets syndrome type 3 (SPS type 3) and enhanced activity of plasminogen activator inhibitor (PAI-1) anomalies. Int J Dermatol. 2014;53(12):1495–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Hegemann B, Helmbold P, Marsch WC. Livedoid vasculitis with ulcerations: the role of antithrombin III deficiency and its therapeutic consequences. Arch Dermatol. 2002;138(6):841–2.PubMedCrossRefGoogle Scholar
  48. 48.
    Criado PR, de Souza Espinel ID, Valentef NS, Alavi A, Kirsner RS. Livedoid vasculopathy and high levels of lipoprotein (a): response to danazol. Dermatol Ther. 2015;28(4):248–53.PubMedCrossRefGoogle Scholar
  49. 49.
    Boyvat A, Kundakci N, Babikir MO, Gurgey E. Livedoid vasculopathy associated with heterozygous protein C deficiency. Br J Dermatol. 2000;143(4):840–2.PubMedCrossRefGoogle Scholar
  50. 50.
    Baccard M, Vignon-Pennamen MD, Janier M, Scrobohaci ML, Dubertret L. Livedo vasculitis with protein C system deficiency. Arch Dermatol. 1992;128(10):1410–1.PubMedCrossRefGoogle Scholar
  51. 51.
    Nakayama T, Mizutani K, Hanamura I, Kato H, Takami A, Takeshita K, et al. Livedoid vasculopathy and popliteal artery occlusion in a patient with protein S deficiency. J Dermatol. 2017;44(2):198–201.PubMedCrossRefGoogle Scholar
  52. 52.
    Song HB, Woo SJ, Jung CK, Lee YJ, Ahn J, Park KH, et al. Acute central retinal artery occlusion associated with livedoid vasculopathy: a variant of Sneddon’s syndrome. Korean J Ophthalmol. 2013;27(5):376–80.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Winchester DS, Drage LA, Davis MD. Response of livedoid vasculopathy to rivaroxaban. Br J Dermatol. 2015;172(4):1148–50.PubMedCrossRefGoogle Scholar
  54. 54.
    Lima RS, Maquine GA, Talhari C, Encarnacao IC, Schettini AP, Santos M. Livedoid vasculopathy as a marker of systemic disease: report of two cases. An Bras Dermatol. 2014;89(5):822–4.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Vasconcelos R, Criado PR, Belda W Jr. Livedoid vasculopathy secondary to high levels of lipoprotein(a). Br J Dermatol. 2011;164(5):1111–3.PubMedCrossRefGoogle Scholar
  56. 56.
    Goerge T, Weishaupt C, Metze D, Nowak-Göttl U, Sunderkötter C, Steinhoff M, et al. Livedoid vasculopathy in a pediatric patient with elevated lipoprotein(a) levels: prompt response to continuous low-molecular-weight heparin. Arch Dermatol. 2010;146(8):927–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Kerk N, Drabik A, Luger TA, Schneider SW, Goerge T. Rivaroxaban prevents painful cutaneous infarctions in livedoid vasculopathy. Br J Dermatol. 2013;168(4):898–9.PubMedCrossRefGoogle Scholar
  58. 58.
    Cooper DL, Bolognia JL, Lin JT. Atrophie blanche in a patient with gamma-heavy-chain disease. Arch Dermatol. 1991;127(2):272–3.PubMedCrossRefGoogle Scholar
  59. 59.
    Noda S, Asano Y, Yamazaki M, Ichimura Y, Tamaki Z, Takekoshi T, et al. Severe livedoid vasculopathy associated with antiphosphatidylserine-prothrombin complex antibody successfully treated with warfarin. Arch Dermatol. 2011;147(5):621–3.PubMedCrossRefGoogle Scholar
  60. 60.
    Hasegawa M, Fujimoto M, Orito H, Matsushita T, Hamaguchi Y, Takehara K. Two cases of livedo vasculopathy with non-criteria antiphospholipid antibodies. J Dermatol. 2012;39(12):1026–30.PubMedCrossRefGoogle Scholar
  61. 61.
    Tabata N, Oonami K, Ishibashi M, Yamazaki M. Livedo vasculopathy associated with IgM anti-phosphatidylserine-prothrombin complex antibody. Acta Derm Venereol. 2010;90(3):313–4.PubMedCrossRefGoogle Scholar
  62. 62.
    Osada S, Kimura Y, Kawana S. Case of livedoid vasculopathy with peripheral neuropathy successfully treated with low-dose warfarin. J Dermatol. 2010;37(1):98–101.PubMedCrossRefGoogle Scholar
  63. 63.
    Klein KL, Pittelkow MR. Tissue plasminogen activator for treatment of livedoid vasculitis. Mayo Clin Proc. 1992;67(10):923–33.PubMedCrossRefGoogle Scholar
  64. 64.
    Gan EY, Tang MB, Tan SH, Chua SH, Tan AW. A ten-year retrospective study on livedo vasculopathy in Asian patients. Ann Acad Med Singap. 2012;41(9):400–6.PubMedGoogle Scholar
  65. 65.
    Feng S, Su W, Jin P, Shao C. Livedoid vasculopathy: clinical features and treatment in 24 Chinese patients. Acta Derm Venereol. 2014;94(5):574–8.PubMedCrossRefGoogle Scholar
  66. 66.
    Acland KM, Darvay A, Wakelin SH, Russell-Jones R. Livedoid vasculitis: a manifestation of the antiphospholipid syndrome? Br J Dermatol. 1999;140(1):131–5.PubMedCrossRefGoogle Scholar
  67. 67.
    Yasue T. Livedoid vasculitis and central nervous system involvement in systemic lupus erythematosus. Arch Dermatol. 1986;122(1):66–70.PubMedCrossRefGoogle Scholar
  68. 68.
    So BJ, Park JB, Yoo MG, Kim IH, Son SW. Successful treatment of livedoid vasculitis with primary antiphospholipid syndrome by using aspirin and low dose warfarin combination therapy. Ann Dermatol. 2015;27(5):614–5.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Sopena B, Perez-Rodriguez MT, Rivera A, Ortiz-Rey JA, Lamas J, Freire-Dapena MC. Livedoid vasculopathy and recurrent thrombosis in a patient with lupus: seronegative antiphospholipid syndrome? Lupus. 2010;19(11):1340–3.PubMedCrossRefGoogle Scholar
  70. 70.
    Ravat FE, Evans AV, Russell-Jones R. Response of livedoid vasculitis to intravenous immunoglobulin. Br J Dermatol. 2002;147(1):166–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Langer F, Eifrig B, Marx G, Stork A, Hegewisch-Becker S, Hossfeld DK. Exacerbation of antiphospholipid antibody syndrome after treatment of localized cancer: a report of two cases. Ann Hematol. 2002;81(12):727–31.PubMedCrossRefGoogle Scholar
  72. 72.
    Miura T, Torinuki W, Tanahashi Y. Atrophie blanche examined with thermography. Tohoku J Exp Med. 1976;119(2):165–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Winkelmann RK. Livedoid vasculitis (segmental hyalinizing vasculitis). Jpn J Dermatol B. 1972;82(3):84–9.PubMedGoogle Scholar
  74. 74.
    Chan Y, Tang W, Lam WY, Loo S, Li S, Au A, et al. A cluster of chilblains in Hong Kong. Hong Kong Med J. 2008;14(3):185–91.PubMedGoogle Scholar
  75. 75.
    Oh YB, Jun JB, Kim CK, Lee CW, Park CK, Kim TY, et al. Mixed connective tissue disease associated with skin defects of livedoid vasculitis. Clin Rheumatol. 2000;19(5):381–4.PubMedCrossRefGoogle Scholar
  76. 76.
    Ishibashi M, Miyamoto J, Nagasaka T, Chen KR. Livedoid vasculopathy with underlying subcutaneous necrotizing venulitis in an asymptomatic hepatitis B virus carrier: is livedoid vasculopathy a true nonvasculitic disorder? Am J Dermatopathol. 2009;31(3):293–6.PubMedCrossRefGoogle Scholar
  77. 77.
    Sankar A, Hinshaw K. Livedoid vasculopathy and pregnancy. Int J Gynaecol Obstet. 2009;107(3):248–9.PubMedCrossRefGoogle Scholar
  78. 78.
    El Khoury J, Taher A, Kurban M, Kibbi AG, Abbas O. Livedoid vasculopathy associated with sickle cell trait: significant improvement on aspirin treatment. Int Wound J. 2012;9(3):344–7.PubMedCrossRefGoogle Scholar
  79. 79.
    Reagin H, Marks E, Weis S, Susa J. Livedoid vasculopathy presenting in a patient with sickle cell disease. Am J Dermatopathol. 2018:1.Google Scholar
  80. 80.
    Agirbasli M, Eren M, Eren F, Murphy SB, Serdar ZA, Seckin D, et al. Enhanced functional stability of plasminogen activator inhibitor-1 in patients with livedoid vasculopathy. J Thromb Thrombolysis. 2011;32(1):59–63.PubMedCrossRefGoogle Scholar
  81. 81.
    • Agirbasli M, Goktay F, Peker I, Gunes P, Aker FV, Akkiprik M. Enhanced mRNA expression of plasminogen activator inhibitor-1 in livedoid vasculopathy lesions. Cardiovasc Ther. 2017;35(3) This study found significantly increased plasminogen activator inhibitor-1 gene expression in livedoid vasculopathy lesions relative to controls suggesting its role in the pathogenesis of livedoid vasculopathy. CrossRefGoogle Scholar
  82. 82.
    Kohler HP, Grant PJ. Plasminogen-activator inhibitor type 1 and coronary artery disease. N Engl J Med. 2000;342(24):1792–801.PubMedCrossRefGoogle Scholar
  83. 83.
    • Espinel D, Di Giacomo TB, Pincelli TP, et al. Analysis of serum levels and cutaneous expression of lipoprotein (a) in 38 patients with livedoid vasculopathy. J Cutan Pathol. 2017;44(12):1033–7. This study found a 10-fold higher expression of lipoprotein(a) immunostaining in the skin lesions and elevated serum levels of this protein in livedoid vasculopathy patients relative to controls, suggesting its role in the pathogenic mechanism of livedoid vasculopathy. PubMedCrossRefGoogle Scholar
  84. 84.
    Spence JD, Koschinsky M. Mechanisms of lipoprotein(a) pathogenicity: prothrombotic, proatherosclerotic, or both? Arterioscler Thromb Vasc Biol. 2012;32(7):1550–1.PubMedCrossRefGoogle Scholar
  85. 85.
    Hajjar KA, Gavish D, Breslow JL, Nachman RL. Lipoprotein(a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis. Nature. 1989;339(6222):303–5.PubMedCrossRefGoogle Scholar
  86. 86.
    Hesse G, Kutzner H. Niedermolekulares heparin zur therapie der ulzerierten capillaritis alba. Phlebologie. 2008;37(5):259–65.CrossRefGoogle Scholar
  87. 87.
    Criado PR, Rivitti EA, Sotto MN, Valente NYS, Aoki V, Carvalho JF, et al. Livedoid vasculopathy: an intringuing cutaneous disease. An Bras Dermatol. 2011;86(5):961–77.PubMedCrossRefGoogle Scholar
  88. 88.
    McCalmont CS, McCalmont TH, Jorizzo JL, White WL, Leshin B, Rothberger H. Livedo vasculitis: vasculitis or thrombotic vasculopathy? Clin Exp Dermatol. 1992;17(1):4–8.PubMedCrossRefGoogle Scholar
  89. 89.
    • Micieli R, Alavi A. Treatment for livedoid vasculopathy: a systematic review. JAMA Dermatol. 2017; Systematic review of case series studying treatment efficacy in livedoid vasculopathy. To date, only case series and case reports have studied management of livedoid vasculopathy. Anticoagulants were the most commonly reported treatment. Google Scholar
  90. 90.
    Chen W, Fan L, Wang Y, Deng X. Treatment application of rivaroxaban in Chinese patients with livedoid vasculopathy. J Pain Res. 2017;10:621–4.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Lee JM, Kim IH. Case series of recalcitrant livedoid vasculopathy treated with rivaroxaban. Clin Exp Dermatol. 2016;41(5):559–61.PubMedCrossRefGoogle Scholar
  92. 92.
    Jimenez-Gallo D, Villegas-Romero I, Rodriguez-Mateos ME, Linares-Barrios M. Treatment of livedoid vasculopathy with rivaroxaban: a potential use of new oral anticoagulants for dermatologists. Actas Dermosifiliogr. 2018;109(3):278–81.PubMedCrossRefGoogle Scholar
  93. 93.
    Drerup C, Goerge T. Prevention of livedoid vasculopathy recurrence by prolonged administration of rivaroxaban. J Eur Acad Dermatol Venereol. 2017;31(12):e532.PubMedCrossRefGoogle Scholar
  94. 94.
    Evans JM, Jensen JD, Sami N. Successful treatment of livedoid vasculopathy with rivaroxaban. JAAD Case Rep. 2015;1(6):340–1.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Saoji V, Madke B. Use of low-dose oral warfarin in three cases of livedoid vasculopathy. Indian J Dermatol. 2017;62(5):508–11.PubMedPubMedCentralGoogle Scholar
  96. 96.
    Murrell DF, Jensen J, O'Keefe EJ. Failure of livedoid vasculitis to respond to tissue plasminogen activator. Arch Dermatol. 1995;131(2):231–2.PubMedCrossRefGoogle Scholar
  97. 97.
    Toth C, Trotter M, Clark A, Zochodne D. Mononeuropathy multiplex in association with livedoid vasculitis. Muscle Nerve. 2003;28(5):634–9.PubMedCrossRefGoogle Scholar
  98. 98.
    Hsiao GH, Chiu HC. Low-dose danazol in the treatment of livedoid vasculitis. Dermatology. 1997;194(3):251–5.PubMedCrossRefGoogle Scholar
  99. 99.
    Hsiao GH, Chiu HC. Livedoid vasculitis. Response to low-dose danazol. Arch Dermatol. 1996;132(7):749–51.PubMedCrossRefGoogle Scholar
  100. 100.
    Herskovitz I, Jaller J, Kirsner R. Two successful cases of combination therapy with rivaroxaban and stanozolol for livedoid vasculopathy. JAAD. 2017;76(6):AB272.Google Scholar
  101. 101.
    Lee SS, Ang P, Tan SH. Clinical profile and treatment outcome of livedoid vasculitis: a case series. Ann Acad Med Singap. 2003;32(6):835–9.PubMedGoogle Scholar
  102. 102.
    Sams WM Jr. Livedo vasculitis. Therapy with pentoxifylline. Arch Dermatol. 1988;124(5):684–7.PubMedCrossRefGoogle Scholar
  103. 103.
    Kern AB. Atrophie blanche. Report of two patients treated with aspirin and dipyridamole. J Am Acad Dermatol. 1982;6(6):1048–53.PubMedCrossRefGoogle Scholar
  104. 104.
    Grob JJ, Bonerandi JJ. Thrombotic skin disease as a marker of the anticardiolipin syndrome. Livedo vasculitis and distal gangrene associated with abnormal serum antiphospholipid activity. J Am Acad Dermatol. 1989;20(6):1063–9.PubMedCrossRefGoogle Scholar
  105. 105.
    Yamamoto M, Danno K, Shio H, Imamura S. Antithrombotic treatment in livedo vasculitis. J Am Acad Dermatol. 1988;18(1 Pt 1):57–62.PubMedCrossRefGoogle Scholar
  106. 106.
    Malaguti MC, Cavallaro T, Speziali L, Zorzi MG, Marangoni S, Morini A. Mononeuritis multiplex associated with primary livedoid vasculopathy: neuropathological evidence of ischemic nerve damage. J Neurol Sci. 2015;351(1–2):214–5.PubMedCrossRefGoogle Scholar
  107. 107.
    Vanness ER, Davis MD, Tefferi A. Cutaneous findings associated with chronic natural killer cell lymphocytosis. Int J Dermatol. 2002;41(12):852–7.PubMedCrossRefGoogle Scholar
  108. 108.
    Vieira R, Bernardes JM, Pinto JA, Costa L. Livedoid vasculopathy—a challenging disease. Acta Reumatol Port. 2016;41(3):273–4.PubMedGoogle Scholar
  109. 109.
    Bennett DD, Ohanian M, Cable CT. Rituximab in severe skin diseases: target, disease, and dose. Clin Pharmacol. 2010;2:135–41.PubMedPubMedCentralGoogle Scholar
  110. 110.
    Zeni P, Finger E, Scheinberg MA. Successful use of rituximab in a patient with recalcitrant livedoid vasculopathy. Ann Rheum Dis. 2008;67(7):1055–6.PubMedCrossRefGoogle Scholar
  111. 111.
    Ray R, Sharma A, Vasudevan B, Sridhar J, Deo R, Mohanty CS. Livedoid vasculopathy with hyperhomocysteinemia responding to hyperbaric oxygen therapy. Indian J Dermatol. 2015;60(5):524.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Banham ND. Livedoid vasculopathy successfully treated with hyperbaric oxygen. Diving Hyperb Med. 2013;43(1):35–6.PubMedGoogle Scholar
  113. 113.
    Bhutani S, Verma R, Verghese G. Livedoid vasculopathy managed with hyperbaric oxygen therapy. Med J Armed Forces India. 2012;68(4):389–91.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Ueno T, Omi T, Uchida E, Yokota H, Kawana S. Evaluation of hyperbaric oxygen therapy for chronic wounds. J Nippon Med Sch. 2014;81(1):4–11.PubMedCrossRefGoogle Scholar
  115. 115.
    Yang CH, Ho HC, Chan YS, Liou LB, Hong HS, Yang LC. Intractable livedoid vasculopathy successfully treated with hyperbaric oxygen. Br J Dermatol. 2003;149(3):647–52.PubMedCrossRefGoogle Scholar
  116. 116.
    Kim EJ, Yoon SY, Park HS, Yoon HS, Cho S. Pulsed intravenous immunoglobulin therapy in refractory ulcerated livedoid vasculopathy: seven cases and a literature review. Dermatol Ther. 2015;28(5):287–90.PubMedCrossRefGoogle Scholar
  117. 117.
    Bounfour T, Bouaziz JD, Bezier M, et al. Intravenous immunoglobulins in difficult-to-treat ulcerated livedoid vasculopathy: five cases and a literature review. Int J Dermatol. 2013;52(9):1135–9.PubMedCrossRefGoogle Scholar
  118. 118.
    Kreuter A, Gambichler T, Breuckmann F, Bechara FG, Rotterdam S, Stücker M, et al. Pulsed intravenous immunoglobulin therapy in livedoid vasculitis: an open trial evaluating 9 consecutive patients. J Am Acad Dermatol. 2004;51(4):574–9.PubMedCrossRefGoogle Scholar
  119. 119.
    Pitarch G, Rodriguez-Serna M, Torrijos A, Oliver V, Fortea JM. Treatment of livedoid vasculopathy with short-cycle intravenous immunoglobulins. Acta Derm Venereol. 2005;85(4):374–5.PubMedGoogle Scholar
  120. 120.
    Schanz S, Ulmer A, Fierlbeck G. Intravenous immunoglobulin in livedo vasculitis: a new treatment option? J Am Acad Dermatol. 2003;49(3):555–6.PubMedCrossRefGoogle Scholar
  121. 121.
    Amital H, Levy Y, Shoenfeld Y. Use of intravenous immunoglobulin in livedo vasculitis. Clin Exp Rheumatol. 2000;18(3):404–6.PubMedGoogle Scholar
  122. 122.
    Levy Y, Sherer Y, George J, Langevitz P, Ahmed A, Bar-Dayan Y, et al. Serologic and clinical response to treatment of systemic vasculitis and associated autoimmune disease with intravenous immunoglobulin. Int Arch Allergy Immunol. 1999;119(3):231–8.PubMedCrossRefGoogle Scholar
  123. 123.
    Tuchinda C, Leenutaphong V, Sudtim S, Lim HW. Refractory livedoid vasculitis responding to PUVA: a report of four cases. Photodermatol Photoimmunol Photomed. 2005;21(3):154–6.PubMedCrossRefGoogle Scholar
  124. 124.
    Lee JH, Choi HJ, Kim SM, Hann SK, Park YK. Livedoid vasculitis responding to PUVA therapy. Int J Dermatol. 2001;40(2):153–7.PubMedCrossRefGoogle Scholar
  125. 125.
    Choi HJ, Hann SK. Livedo reticularis and livedoid vasculitis responding to PUVA therapy. J Am Acad Dermatol. 1999;40(2 Pt 1):204–7.PubMedCrossRefGoogle Scholar
  126. 126.
    Mofarrah R, Aberer W, Aberer E. Treatment of livedoid vasculopathy with alprostadil (PGE-1): case report and review of published literature. J Eur Acad Dermatol Venereol. 2013;27(2):e252–4.PubMedCrossRefGoogle Scholar
  127. 127.
    Furukawa F, Mizawa M, Makino T, Shimizu T. Efficacy of new low-dose oral anticoagulants in recalcitrant livedoid vasculopathy. BMJ Case Rep. 2017;2017Google Scholar
  128. 128.
    Fairfax AJ, Ibbotson RM. Effect of danazol on the biochemical abnormality of inherited antithrombin III deficiency. Thorax. 1985;40(9):646–50.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Gonzalez-Santiago TM, Davis MD. Update of management of connective tissue diseases: livedoid vasculopathy. Dermatol Ther. 2012;25(2):183–94.CrossRefPubMedGoogle Scholar
  130. 130.
    Zampeli E, Moutsopoulos HM. Livedoid vasculopathy. Arthritis Rheum. 2017;69(10):2096.CrossRefGoogle Scholar
  131. 131.
    Ibbotson SH, Layton AM, Davies JA, Goodfield MJ. The effect of aspirin on haemostatic activity in the treatment of chronic venous leg ulceration. Br J Dermatol. 1995;132(3):422–6.PubMedCrossRefGoogle Scholar
  132. 132.
    Hankey GJ, Eikelboom JW. Homocysteine and vascular disease. Lancet. 1999;354(9176):407–13.PubMedCrossRefGoogle Scholar
  133. 133.
    den Heijer M, Koster T, Blom HJ, Bos GMJ, Briët E, Reitsma PH, et al. Hyperhomocysteinemia as a risk factor for deep-vein thrombosis. N Engl J Med. 1996;334(12):759–62.CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Faculty of MedicineUniversity of TorontoTorontoCanada
  2. 2.Department of Medicine, Division of DermatologyWomen’s College HospitalTorontoCanada

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