Livedoid Vasculopathy 

  • Author: Noah S Scheinfeld, MD, JD, FAAD; Chief Editor: William D James, MD   more...
 
Updated: Aug 1, 2011
 

Background

Livedoid vasculopathy (LV), or livedoid vasculitis, is a hyalinizing vascular disease characterized by thrombosis and ulceration of the lower extremities. Livedoid vasculopathy can evolve into a dermatologic finding termed atrophie blanche (AB). Livedoid vasculopathy is a distinct condition that is not usually the result of other diseases, as Jorizzo elegantly noted in 1998.[1]

Biopsy specimens of livedoid vasculopathy aid in diagnosing this condition, but they are not pathognomonic. The skin manifests with segmental hyalinizing vascular involvement of thickened dermal blood vessels, endothelial proliferation, and focal thrombosis without nuclear dust. No true vasculitis is evident. While direct immunofluorescence study reveals immunoglobulin and complement components in the superficial, mid-dermal, and deep dermal vessels, this is merely the result of spongelike absorption of immune components in the thickened vessels. They do not appear to be pathogenic. Pathogenesis involves hyalinization and thrombosis rather than leukocytoclastic vasculitis.

In 1955, Feldaker et al[2] described what is now termed livedoid vasculopathy as livedo reticularis with summer ulcerations. In 1967, Bard and Winkelmann[3] used the terms segmental hyalinizing vasculitis and livedo vasculitis to describe livedoid vasculopathy.

In 1998, Papi et al[4] noted that platelet and lymphocyte activation was present in livedoid vasculopathy, whereas the levels of inflammatory mediators were in the reference range; in particular, they noted increased expression of platelet P-selectin.

Hairston et al[5] reviewed the records of 42 patients with proven livedoid vasculopathy. The following is a summary of the epidemiological and testing data:

  • Approximately 71% were women
  • Mean age of 45 years
  • Age range of 10-85 years
  • Bilateral lower extremity disease in 80.8%
  • Ulceration in 68.9%
  • Atrophie blanche in 71.1%
  • Decreased transcutaneous oximetry measurements in 74.1% of patients tested
  • Mutated factor V Leiden mutation (heterozygous) in 22.2%
  • Decreased activity for protein C or protein in 13.3%
  • Prothrombin G20210A gene mutation in 8.3%
  • Lupus anticoagulant in 17.9%
  • Anticardiolipin antibodies in 28.6%
  • Increased homocysteine levels in 14.3%
  • Biopsy specimens showing intraluminal thrombosis in 97.8%
  • Biopsy specimens with direct immunofluorescence test results showing multiple vascular conjugates in 86.1%
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Pathophysiology

While the etiology of livedoid vasculopathy is not yet fully defined, it likely has a procoagulant pathogenesis.[5] Factor V Leiden mutation, heterozygous protein C deficiency,[6] and other inherited hypercoagulable states have been linked to livedoid vasculopathy.[7] In particular, states such as hyperhomocysteinemia, which results in increased clotting, plays a role in livedoid vasculopathy.[8] Plasminogen activator inhibitor (PAI)–1 is an important inhibitor of the fibrinolytic system, and the PAI-1 promoter 4G/4G genotype, in which PAI-1 is increased, has been liked to livedoid vasculopathy.[7]

The histology of livedoid vasculopathy evolves according to the temporal stage of the lesion. Atrophie blanche is a scarring condition of white stellate scars that is an end stage of livedoid vasculopathy.

Most commonly, livedoid vasculopathy shows fibrin deposition within both the wall and the lumen of affected vessels. The absence of a substantial perivascular infiltrate or leukocytoclasia argues against a vasculitis, being more in keeping with a thrombo-occlusive process.

The underlying mechanism of the development of livedoid vasculopathy may be related to (1) the development of a fibrin cuff, (2) white-cell trapping, (3) microthrombi, (4) a defect of endothelial cell plasminogen activator, (5) platelet dysfunction, and (6) enhanced fibrin formation. The following is a summary of the excellent discussion of these mechanisms by Maessen-Visch et al[9] in 1999.

Browse and Burnand[10] posited the fibrin cuff theory. The fibrin cuff theory postulates that because of chronic venous compromise, fibrinogen leaks from the capillaries. This fibrinogen coagulates and hardens to form a fibrin cuff. This cuff surrounds the capillaries. The cuff establishes a barrier that prevents oxygen and nutrients from reaching the skin. However, Maessen-Visch et al[9] note that fibrin is an effective barrier to prevent the diffusion of oxygen to tissue. The cuffs then are an artifact rather than a seal. The fibrin cuffs are more an indication of disturbed microcirculation rather than an etiologic factor in chronic venous insufficiency; therefore, this theory is of uncertain accuracy.

In 1988, Coleridge Smith et al[11] suggested the white-cell trapping theory. In this schema, white cells adhere (trap) to the endothelium of the capillaries as a result of venous hypertension. This results in the induction of proteolytic enzymes and superoxide metabolites. These enzymes and metabolites cause tissue destruction. This molecular degrading effect on tissue appears to be a nonimmunologic phenomenon. Its etiology is due to the low flow in the wide capillaries. No up-regulation of binding molecules, such as intercellular adhesion molecule, vascular cellular adhesion molecule, and endothelial leucocyte adhesion molecule, occurs. A defect of endothelial cell plasminogen activator exists in some patients with livedoid vasculopathy. However, at least 20% of the 118 control subjects showed the same values as patients with livedoid vasculopathy.

Tissue-type plasminogen activator (tPA) levels appear to be lower in patients with livedoid vasculopathy. The average plasma level of releasable tPA was only 0.03 IU/mL in one study, versus an average tPA level of 0.70 IU/mL in 118 healthy controls.[12] Furthermore, Klein and Pittelkow[13] reported a high incidence of defective release of tPA and increased levels of PAI and a high incidence of antiphospholipid antibodies in patients with livedoid vasculopathy. levels of tPA in the reference range were found in patients with chronic venous insufficiency and atrophie blanche or lipodermatosclerosis.

Other evidence has implicated platelet dysfunction; one study noted that 7 patients with atrophie blanche and livedoid vasculopathy had increased platelet aggregation. These 7 patients were treated successfully with antiplatelet therapy.[14] The value of this study is limited because it was not controlled or designed to evaluate these factors and enzyme levels.

Enhanced fibrin formation, as evidenced by elevated levels of total fibrin-related antigen and D-dimer, has also been suggested as the cause for livedoid vasculopathy. This theory also needs to be tested via double-blinded studies. As of yet, well-crafted and adequate studies have not been performed.

Irani-Hakime et al noted livedoid vasculopathy associated with combined prothrombin G20210A and factor V (Leiden) heterozygosity and MTHFR C677T homozygosity, showing a range of thrombotic states can cause livedoid vasculopathy.[15]

Livedoid vasculopathy seems to be primarily an occlusive condition rather than an inflammatory condition.

Livedoid vasculopathy related to elevated levels of lipoprotein(a) has been noted.[16]

Also note the completed clinical trial, Correlation of Genetic Polymorphism and Livedo Vasculitis.

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Epidemiology

Frequency

United States

Livedoid vasculopathy is an uncommon disorder in the United States.

International

Livedoid vasculopathy is an uncommon condition worldwide.

Mortality/Morbidity

Livedoid vasculopathy, although painful, is not associated with any loss of life or limb.

Sex

Women are affected by livedoid vasculopathy more often than men. Livedoid vasculopathy can occur during pregnancy when levels of protein C and S drop.[17]

Age

Livedoid vasculopathy lesions can occur at any age, but livedoid vasculopathy is most commonly a disease of adulthood.

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Contributor Information and Disclosures
Author

Noah S Scheinfeld, MD, JD, FAAD  Assistant Clinical Professor, Department of Dermatology, Columbia University College of Physicians and Surgeons; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, and New York Eye and Ear Infirmary; Private Practice

Noah S Scheinfeld, MD, JD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Optigenex Consulting fee Independent contractor

Specialty Editor Board

Timothy McCalmont, MD  Director, UCSF Dermatopathology Service, Professor of Clinical Pathology and Dermatology, Departments of Pathology and Dermatology, University of California at San Francisco; Editor-in-Chief, Journal of Cutaneous Pathology

Timothy McCalmont, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Society of Dermatopathology, California Medical Association, College of American Pathologists, and United States and Canadian Academy of Pathology

Disclosure: Apsara Consulting fee Independent contractor

Michael J Wells, MD  Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Jeffrey Meffert, MD  Assistant Clinical Professor of Dermatology, University of Texas School of Medicine at San Antonio

Jeffrey Meffert, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists, and Texas Dermatological Society

Disclosure: Nothing to disclose.

Glen H Crawford, MD  Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital

Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD  Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System

William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology

Disclosure: Elsevier Royalty Other

Acknowledgments

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Richard H. Musgnug, MD, to the development and writing of this article.

References

  1. Jorizzo JL. Livedoid vasculopathy: what is it?. Arch Dermatol. Apr 1998;134(4):491-3. [Medline].

  2. Feldaker M, Hines EA Jr, Kierland RR. Livedo reticularis with summer ulcerations. AMA Arch Derm. Jul 1955;72(1):31-42. [Medline].

  3. Bard JW, Winkelmann RK. Livedo vasculitis. Segmental hyalinizing vasculitis of the dermis. Arch Dermatol. Nov 1967;96(5):489-99. [Medline].

  4. Papi M, Didona B, De Pita O, et al. Livedo vasculopathy vs small vessel cutaneous vasculitis: cytokine and platelet P-selectin studies. Arch Dermatol. Apr 1998;134(4):447-52. [Medline].

  5. Hairston BR, Davis MD, Pittelkow MR, Ahmed I. Livedoid vasculopathy: further evidence for procoagulant pathogenesis. Arch Dermatol. Nov 2006;142(11):1413-8. [Medline].

  6. Baccard M, Vignon-Pennamen MD, Janier M, Scrobohaci ML, Dubertret L. Livedo vasculitis with protein C system deficiency. Arch Dermatol. Oct 1992;128(10):1410-1. [Medline].

  7. 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. Nov 2006;142(11):1466-9. [Medline].

  8. Meiss F, Marsch WC, Fischer M. Livedoid vasculopathy. The role of hyperhomocysteinemia and its simple therapeutic consequences. Eur J Dermatol. Mar-Apr 2006;16(2):159-62. [Medline].

  9. Maessen-Visch MB, Koedam MI, Hamulyák K, Neumann HA. Atrophie blanche. Int J Dermatol. Mar 1999;38(3):161-72. [Medline].

  10. Browse NL, Burnand KG. The cause of venous ulceration. Lancet. Jul 31 1982;2(8292):243-5. [Medline].

  11. Coleridge Smith PD, Thomas P, Scurr JH, Dormandy JA. Causes of venous ulceration: a new hypothesis. Br Med J (Clin Res Ed). Jun 18 1988;296(6638):1726-7. [Medline].

  12. Pizzo SV, Murray JC, Gonias SL. Atrophie blanche. A disorder associated with defective release of tissue plasminogen activator. Arch Pathol Lab Med. Jun 1986;110(6):517-9. [Medline].

  13. Klein KL, Pittelkow MR. Tissue plasminogen activator for treatment of livedoid vasculitis. Mayo Clin Proc. Oct 1992;67(10):923-33. [Medline].

  14. Drucker CR, Duncan WC. Antiplatelet therapy in atrophie blanche and livedo vasculitis. J Am Acad Dermatol. Sep 1982;7(3):359-63. [Medline].

  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. Aug 2008;26(1):31-4. [Medline].

  16. Vasconcelos R, Criado PR, Belda W Jr. Livedoid vasculopathy secondary to high levels of lipoprotein(a). Br J Dermatol. May 2011;5:1111-3. [Medline].

  17. Sankar A, Hinshaw K. Livedoid vasculopathy and pregnancy. Int J Gynaecol Obstet. 2009;107:248-9. [Medline].

  18. Toth C, Trotter M, Clark A, Zochodne D. Mononeuropathy multiplex in association with livedoid vasculitis. Muscle Nerve. Nov 2003;28(5):634-9. [Medline].

  19. Marzano AV, Vanotti M, Alessi E. Widespread livedoid vasculopathy. Acta Derm Venereol. 2003;83(6):457-60. [Medline].

  20. Cardoso R, Goncalo M, Tellechea O, et al. Livedoid vasculopathy and hypercoagulability in a patient with primary Sjögren's syndrome. Int J Dermatol. Apr 2007;46(4):431-4. [Medline].

  21. Okada E, Nagai Y, Ishikawa O. A case of widespread livedoid vasculopathy with pain but no systemic symptoms. Acta Derm Venereol. 2008;88(3):298-9. [Medline].

  22. Verma R, Hadid TH, Dhamija R, Moad JC, Loehrke ME. Livedoid vasculopathy in a woman with multiple myeloma. South Med J. Aug 2010;103(8):848-9. [Medline].

  23. 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. Jul 21 2010;[Medline].

  24. Anavekar NS, Kelly R. Heterozygous prothrombin gene mutation associated with livedoid vasculopathy. Australas J Dermatol. May 2007;48(2):120-3. [Medline].

  25. Ackerman AB, Chongchitnant N, Sanchez J. Histologic Diagnosis of Inflammatory Skin Diseases: An Algorithmic Method Based on Pattern Analysis. 2nd ed. Baltimore, Md: Williams & Wilkins; 1997.

  26. Sams WM Jr. Livedo vasculitis. Therapy with pentoxifylline. Arch Dermatol. May 1988;124(5):684-7. [Medline].

  27. Hairston BR, Davis MD, Gibson LE, Drage LA. Treatment of livedoid vasculopathy with low-molecular-weight heparin: report of 2 cases. Arch Dermatol. Aug 2003;139(8):987-90. [Medline].

  28. Yang CH, Ho HC, Chan YS, Liou LB, Hong HS, Yang LC. Intractable livedoid vasculopathy successfully treated with hyperbaric oxygen. Br J Dermatol. Sep 2003;149(3):647-52. [Medline].

  29. 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. Feb 2006;154(2):251-5. [Medline].

  30. Kern AB. Atrophie blanche. Report of two patients treated with aspirin and dipyridamole. J Am Acad Dermatol. Jun 1982;6(6):1048-53. [Medline].

  31. Purcell SM, Hayes TJ. Nifedipine treatment of idiopathic atrophie blanche. J Am Acad Dermatol. May 1986;14(5 Pt 1):851-4. [Medline].

  32. Antunes J, Filipe P, André 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;90:91-2. [Medline].

  33. Amital H, Levy Y, Shoenfeld Y. Use of intravenous immunoglobulin in livedo vasculitis. Clin Exp Rheumatol. May-Jun 2000;18(3):404-6. [Medline].

  34. Browning CE, Callen JP. Warfarin therapy for livedoid vasculopathy associated with cryofibrinogenemia and hyperhomocysteinemia. Arch Dermatol. Jan 2006;142(1):75-8. [Medline].

  35. 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 Dermatolog Treat. 2008;19(2):121-3. [Medline].

  36. Davis MD, Wysokinski WE. Ulcerations caused by livedoid vasculopathy associated with a prothrombotic state: Response to warfarin. J Am Acad Dermatol. Mar 2008;58(3):512-5. [Medline].

  37. Heine KG, Davis GW. Idiopathic atrophie blanche: treatment with low-dose heparin. Arch Dermatol. Aug 1986;122(8):855-6. [Medline].

  38. 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. May 2011;5:621-3. [Medline].

  39. Bisalbutra P, Kullavanijaya P. Sulfasalazine in atrophie blanche. J Am Acad Dermatol. Feb 1993;28(2 Pt 1):275-6. [Medline].

  40. Bollinger A. [White atrophy: skin infarction of various pathogeneses?]. Vasa. 1981;10(1):67-9. [Medline].

  41. Bollinger A, Leu AJ. Evidence for microvascular thrombosis obtained by intravital fluorescence videomicroscopy. Vasa. 1991;20(3):252-5. [Medline].

  42. Bugatti L, Filosa G, Nicolini M, Filosa A, Verdolini R. Atrophie blanche associated with interferon-alfa adjuvant therapy for melanoma: a cutaneous side effect related to the procoagulant activity of interferon?. Dermatology. 2002;204(2):154. [Medline].

  43. Callen JP. Livedoid vasculopathy: what it is and how the patient should be evaluated and treated. Arch Dermatol. Nov 2006;142(11):1481-2. [Medline].

  44. Frances C, Barete S. Difficult management of livedoid vasculopathy. Arch Dermatol. Aug 2004;140(8):1011. [Medline].

  45. Grattan CE, Burton JL. Antiphospholipid syndrome and cutaneous vasoocclusive disorders. Semin Dermatol. Sep 1991;10(3):152-9. [Medline].

  46. Kluken N, Zabel M. [Pathologic anatomy of white atrophy]. Phlebologie. Jul-Sep 1986;39(3):561-6. [Medline].

  47. Krasner D. Painful venous ulcers: themes and stories about their impact on quality of life. Ostomy Wound Manage. Sep 1998;44(9):38-42, 44, 46 passim. [Medline].

  48. Leonard A, Pomeranz MK, Franks AG Jr. A case of livedoid vasculopathy in a 22-year-old man. J Drugs Dermatol. Nov-Dec 2004;3(6):678-9. [Medline].

  49. Lewerenz V, Burchardt T, Büchau A, Ruzicka T, Megahed M. [Livedoid vasculopathy with heterozygous factor V Leiden mutation and sticky platelet syndrome]. Hautarzt. Apr 2004;55(4):379-81. [Medline].

  50. McCalmont CS, McCalmont TH, Jorizzo JL, White WL, Leshin B, Rothberger H. Livedo vasculitis: vasculitis or thrombotic vasculopathy?. Clin Exp Dermatol. Jan 1992;17(1):4-8. [Medline].

  51. Millan G. Les atrophies cutane'es syphilitques. Bull Soc Fr Derm Syph. 1929;36:865-71.

  52. Milstone LM, Braverman IM. PURPLE (oops! Atrophie blanche) revisited. Arch Dermatol. Dec 1998;134(12):1634. [Medline].

  53. Pascarella L, Bergan JJ, Mekenas LV. Severe chronic venous insufficiency treated by foamed sclerosant. Ann Vasc Surg. Jan 2006;20(1):83-91. [Medline].

  54. Phillips T, Stanton B, Provan A, Lew R. A study of the impact of leg ulcers on quality of life: financial, social, and psychologic implications. J Am Acad Dermatol. Jul 1994;31(1):49-53. [Medline].

  55. Schroeter AL, Diaz-Perez JL, Winkelmann RK, Jordan RE. Livedo vasculitis (the vasculitis of atrophie blanche). Immunohistopathologic study. Arch Dermatol. Feb 1975;111(2):188-93. [Medline].

  56. Shornick JK, Nicholes BK, Bergstresser PR, Gilliam JN. Idiopathic atrophie blanche. J Am Acad Dermatol. Jun 1983;8(6):792-8. [Medline].

  57. Suarez SM, Paller AS. Atrophie blanche with onset in childhood. J Pediatr. Nov 1993;123(5):753-5. [Medline].

  58. Suster S, Ronnen M, Bubis JJ, Schewach-Millet M. Familial atrophie blanche-like lesions with subcutaneous fibrinoid vasculitis. The Georgian ulcers. Am J Dermatopathol. Oct 1986;8(5):386-91. [Medline].

  59. Valencia IC, Falabella A, Kirsner RS, Eaglstein WH. Chronic venous insufficiency and venous leg ulceration. J Am Acad Dermatol. Mar 2001;44(3):401-21; quiz 422-4. [Medline].

  60. Vowden K. Lipodermatosclerosis and atrophie blanche. J Wound Care. Oct 1998;7(9):441-3. [Medline].

 
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