Livedoid Vasculopathy

Updated: Apr 23, 2020
  • Author: Fnu Nutan, MD, FACP; Chief Editor: William D James, MD  more...
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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 white scars termed atrophie blanche (AB), as shown in the image below. Livedoid vasculopathy is a distinct condition that is not usually the result of other diseases, as Jorizzo elegantly noted in 1998. [1] Conditions associated with livedoid vasculopathy include inherited thrombophilias, acquired thrombophilias, autoimmune connective-tissue disease, and neoplasms. [2]

Atrophie blanche in livedoid vasculopathy. Courtes Atrophie blanche in livedoid vasculopathy. Courtesy of DermNet New Zealand (

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 [3] described what is now termed livedoid vasculopathy as livedo reticularis with summer ulcerations. In 1967, Bard and Winkelmann [4] used the terms segmental hyalinizing vasculitis and livedo vasculitis to describe livedoid vasculopathy.

In 1998, Papi et al [5] 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 [6] 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 S 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%



It is commonly accepted that livedoid vasculopathy is caused by thrombotic occlusion of the cutaneous microcirculation, which can restrict blood supply to tissues. [7]

Livedoid vasculopathy likely has a procoagulant pathogenesis. [6] Factor V Leiden mutation, [8] heterozygous protein C deficiency, [9] and other inherited hypercoagulable states have been linked to livedoid vasculopathy. [10] In particular, states such as hyperhomocysteinemia, which results in increased clotting, plays a role in livedoid vasculopathy. [11] 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. [10]

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. 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.

Browse and Burnand [12] proposed 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 [13] 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 [14] 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. [15] Furthermore, Klein and Pittelkow [16] 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. [17] 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. [18]

Yang et al suggested an association between reduced endothelial function of the brachial artery and livedoid vasculopathy. The main cause of this dysfunction could be attributed to low nitrous oxide levels, as nitrous oxide is involved in the inhibition of platelet aggregation and fibrin. [19]

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

The relationship between livedoid vasculopathy and elevated levels of lipoprotein(a) has been noted. [20]

Livedoid vasculopathy was correlated with increased activity of plasminogen activator inhibitor (PAI-1) pathology and sticky platelets syndrome type III (also referred to as SPS type III). [21]

Livedoid vasculopathy may also be related to antithrombin III deficiency or other anticoagulant deficiencies, leading to abnormalities in the fibrinolytic pathway. [2]

In 2014, Criado noted three patients with high plasma levels of factor VIII:C activity and other associated thrombophilic factors in patients with chronic leg ulcers and livedoid vasculopathy. [22]




United States

Livedoid vasculopathy is an uncommon disorder in the United States and occurs in approximately 1 in 100,000 people in North America. [7]


Livedoid vasculopathy is an uncommon condition worldwide. In China, a study of 21 patients was performed. [23] The peak age at beginning of disease was 14-20 years and the ratio of female to male was 3:1. This was a younger age of onset than in previous studies. More than 85% demonstrated exacerbation in the summer, with ulcer formation; 58.33% demonstrated antiphospholipid antibodies; and 71.43% demonstrated multivalent insect antigens hypersensitivity. [23]

In Brazil, livedoid vasculopathy linked with peripheral neuropathy was noted in 2 cases. [24]


Women are affected by livedoid vasculopathy more often than men. The ratio of female to male is 2.4-3 females for every male. [25] Livedoid vasculopathy can occur during pregnancy when levels of protein C and S drop. [26]


Livedoid vasculopathy lesions can occur at any age, but livedoid vasculopathy is most commonly a disease of adulthood. An interesting case of livedoid vasculopathy occurred in a child in an area on the leg where a cutaneous hemangioma had been present. The average age at diagnosis is 32 years and it is most prevalent in people aged 15-50 years. [7]



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


Patient Education

Patients must understand that livedoid vasculopathy is a chronic condition whose effects can sometimes be improved by medications. When it resolves, it leaves white stellate scars that have been termed atrophie blanche.