AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Background

Livedoid vasculopathy (LV), or livedoid vasculitis, is a disease characterized by ulceration of the lower extremities. It can evolve into a dermatologic finding termed atrophie blanche (AB). LV is a distinct condition that is not usually the result of other diseases, as Jorizzo elegantly noted in 1998.¹

Biopsy specimens of LV 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. Direct immunofluorescence study reveals immunoglobulin and complement components in the superficial, mid-dermal, and deep dermal vessels.

In 1955, Feldaker et al² described what is now termed LV as livedo reticularis with summer ulcerations. In 1967, Bard and Winkelmann³ used the terms segmental hyalinizing vasculitis and livedo vasculitis to describe LV.

In 1998, Papi et al⁴ noted that platelet and lymphocyte activation was present in LV, whereas the levels of inflammatory mediators were in the reference range; in particular, they noted increased expression of platelet P-selectin.

Hairston et al⁵ reviewed the records of 42 patients with proven LV. 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%
• AB 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%

An article of interest available through Medscape is An Analysis of the Effectiveness of Skin Grafting to Treat Chronic Venous Leg Ulcers. Medscape CME courses of interest are Consensus Statement Describes Dressings for Acute and Chronic Wound Management and VEITHSymposium 2007: How to Use Evidence-Based Medicine in Wound Care.

Pathophysiology

While the etiology of LV 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 LV.⁷ In particular, states such as hyperhomocysteinemia, which results in increased clotting, plays a role in LV.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 LV.⁷

The histology of LV evolves according to the temporal stage of the lesion. AB is a scarring condition of white stellate scars that is an end stage of LV. Venous stasis and other conditions, such as leukocytoclastic vasculitis, can lead to identical white scars on the legs.

Most commonly, LV 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 LV 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 al⁹ in 1999.

Browse and Burnand¹⁰ 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 al⁹ 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 al¹¹ 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 LV. However, at least 20% of the 118 control subjects showed the same values as patients with LV.

Tissue-type plasminogen activator (tPA) levels appear to be lower in patients with LV. 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 Pittelkow¹³ reported a high incidence of defective release of tPA and increased levels of PAI and a high incidence of antiphospholipid antibodies in patients with LV. levels of tPA in the reference range were found in patients with chronic venous insufficiency and AB or lipodermatosclerosis.

Other evidence has implicated platelet dysfunction; one study noted that 7 patients with AB and LV 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 LV. This theory also needs to be tested via double-blinded studies. As of yet, well-crafted and adequate studies have not been performed.

LV seems to be primarily an occlusive condition rather than an inflammatory condition.

Frequency

United States

LV is an uncommon disorder in the United States.

International

LV is an uncommon condition worldwide.

Mortality/Morbidity

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

Sex

Women are affected more often than men.

Age

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

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

History

In LV, the initial findings are typically painful purpuric macules or papules on the ankles and the adjacent dorsum of the feet. Patients may have a history of livedo reticularis on their lower legs. The history may help exclude other diagnostic considerations.

• Medium-sized vasculitides, such as polyarteritis nodosa (PAN), occasionally present with ulceration, resulting in ivory-white, stellate scarring on the lower limbs. These conditions may potentially be misdiagnosed as LV.
• LV is not associated with edema or venous insufficiency, whereas stasis dermatitis with ulceration is usually not painful and is associated with obvious edema and signs of venous insufficiency.
• Patients with LV may have a history of recurrent leg ulcerations. Such patients can have deficiencies in a variety of blood factors (eg, factor V Leiden, protein C). The factor V Leiden mutation is more frequent in patients with venous leg ulceration than in control subjects and the general population. Patients with the factor V Leiden mutation have an increased risk of developing deep venous thrombosis and recurrent leg ulceration. Patients may also have a history of increased plasma homocysteine levels, abnormalities in fibrinolysis, and increased platelet activation.
• LV is not particularly painful, whereas hypertensive ischemic ulcers are painful but are usually larger and lack telangiectatic purple borders.
• History and careful follow-up care can rule out traumatic ulcers and distinguish them from LV.
• Chronic periarteritis nodosa may be associated with painful ulcerations; however, the associated nodules should differentiate chronic periarteritis nodosa from LV.
• In 2003, Toth et al¹⁵ noted mononeuropathy multiplex in association with livedoid vasculitis.
• In 2003, Marzano et al¹⁶ described a 37-year-old woman with a 13-year history of widespread livedo reticularis and recurrent, painful, ulcerative skin lesions. The recurrent ulcerations involved almost the entire body surface. In addition, malar erythema and edema, nonscarring alopecia, and fever were also associated with this patient's condition. Routine laboratory data, immunological investigations, and coagulation parameters were normal or negative.
• In 2007, Cardoso et al¹⁷ noted LV and hypercoagulability in a patient with primary Sjögren syndrome.

Physical

The initial lesions of LV, which often appear in clusters or groups, eventually ulcerate over a period of months and years and form irregular patterns of superficial ulcers. When the ulcers finally heal, they leave behind atrophic porcelain-white scars, which are AB.

• Patients with LV can manifest with livedo reticularis before ulceration, with ulcerations, or with no ulcerations.
• Patients with LV can have Raynaud phenomenon and acrocyanosis.
• Lipodermatosclerosis can be associated with LV.
• Patients who have systemic diseases, such as lupus, rheumatoid arthritis, and Klinefelter syndrome, that can result in skin ulcers can manifest with AB-like lesions. These patients do not have LV.

Causes

The etiology of LV is unknown.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Other Problems to be Considered

Polyarteritis nodosa
Traumatic ulcerations
Ulcerations of arterial insufficiency
Ulcerations of collagen vascular disease

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Lab Studies

• No specific laboratory examinations allow the physician to make a definitive diagnosis of LV, although levels of platelet P-selectin and endothelial thrombomodulin are elevated. Tests that assess the causes of diseases that result in lower leg ulcers can be used to diagnose other diseases but not LV.
• Anavekar and Kelly¹⁸ noted a heterozygous prothrombin gene mutation associated with LV.

Imaging Studies

• Evaluation of a patient can include appropriate imaging studies to evaluate for venous and arterial peripheral vascular disease. For example, venous Doppler studies can be useful in evaluating the disease.
• Microcirculation can be studied by capillary microscopy, transcutaneous oxygen measurements, laser Doppler flowmetry, laser Doppler perfusion imaging, and microlymphography.

Procedures

• A skin biopsy can be used to evaluate this condition.

Histologic Findings

The findings of LV are summarized in Histologic Diagnosis of Inflammatory Skin Diseases: An Algorithmic Method Based on Pattern Analysis by Ackerman et al.¹⁹

Histopathologic findings in the early stage include the following:

• Sparse perivascular infiltrate of lymphocytes
• Interstitial infiltrate of neutrophils
• Fibrin within the walls and fibrin thrombi within the lumen of venules in the upper part of the dermis (most cases)
• Involvement of the lower half of the dermis (sometimes)

Histopathologic findings at the full stage of disease include the following:

• Moderately dense, superficial and deep perivascular infiltrate of lymphocytes
• Sparse neutrophils in the upper dermis
• Fibrin in the walls of venules, in particular in the upper dermis
• Thrombi occluding the lumen of venules in the upper dermis
• Fibrin in the wall and thrombi in the lumen of the same venules in one or more venules
• Large numbers of extravasated red blood cells in the upper part of the dermis
• Edema of the papillary dermis
• Spongiosis and ballooning sometimes resulting in intraepidermal vesiculation
• Epidermal necrosis (sometimes)

Histopathologic findings in the late stage in which lesions of LV appear include the following:

• Sparse infiltrate of lymphocytes mostly in the upper part of the dermis
• Sclerosis in the upper part of the dermis
• Numerous telangiectases in the upper part of the dermis
• Epidermis thinned markedly and largely lacking rete ridges

Direct immunofluorescence staining typically demonstrates immunoglobulin and complement components in the superficial, mid-dermal, and deep dermal vasculature. The granular immunofluorescence staining pattern, typical of immune complex disease, is not seen.

Electron microscopy shows dilatation of capillaries (with a diameter up to 100 μm), with a thin endothelium, together with obliterated capillaries. Vessels are present in a dense, fibrotic connective tissue. Fibrin deposition with occlusion of the lumina of superficial blood vessels can occur. Erythrocytes and platelets are noted as being trapped within the fibrin. In older lesions, endothelial cells are replaced by heavy fibrin depositions.

Pathologic features vary with the stage of evolution of LV. In the early purpuric stage, fibrinoid material may be observed in the upper dermis in the capillary walls and the lumina. Endothelial proliferation and thickened walls are also noted. Deeper dermal and subcutaneous vessels are not involved in this stage.

In the late scarring phase of LV, which appears as AB, the epidermis is thinned and the fibrinoid material has replaced the dermal vessels. Little or no cellular infiltrate is present. The pattern of involvement may vary; in some patients, the upper dermis is more involved than the deeper dermis, and, in other cases, the deeper layers show more of the changes mentioned above.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical Care

While ruling out the various disease states that have been associated with LV, physicians can offer a number of therapies that have been very helpful in reducing pain and ulceration. Instituting treatment as soon as possible is best.

• Pentoxifylline (Trental) (400 mg 3 times/d) may be effective. Pentoxifylline is believed to enhance the blood flow in the capillaries. The blood flow enhancement is attributed to making red blood cells more flexible and thereby reducing viscosity.²⁰
• In 2003, Hairston et al²¹ described treatment of LV with low molecular weight heparin (LMWH).
• As reported by Yang et al²² in 2003, intractable LV was successfully treated with hyperbaric oxygen therapy. Additionally, Juan et al²³ reported a study of 12 subjects with active LV. Subjects received hyperbaric oxygen therapy 5 times/wk. Eight completed the study. Resumption of ambulation and reduction of analgesics were achieved after an average of 4.9 hyperbaric oxygen therapy sessions. Leg ulcers healed completely in these 8 subjects at a mean of 3.4 weeks (range, 2-5 wk). Six patients had relapses of ulceration and responded to additional hyperbaric oxygen therapy. No patients had adverse effects.
• Also in 2003, Marzano et al¹⁶ noted a good clinical response was obtained using intravenous methylprednisolone combined with pentoxifylline for wide spread LV.
• Dipyridamole (Persantine) (75 mg 4 times/d) with up to 325 mg of aspirin per day is reported to reduce pain after 3-6 weeks of therapy. Similar results have been reported using 50 mg of dipyridamole 3 times a day and 325 mg of aspirin once a day.²⁴ Note that aspirin is not to be administered in conjunction with coumarin anticoagulants. Dipyridamole is not considered safe in children or breastfeeding mothers.
• Nifedipine (Procardia) (20 mg 3 times/d) is reported to maintain perfusion in the superficial vessels; therefore, the deposition of fibrin in the vessel walls is impeded.²⁵
• Deng et al⁷ noted that LV associated with PAI-1 promoter homozygosity (4G/4G) was effectively abated with tPA.
• Some reports have noted that intravenous immunoglobulin can be useful in treating AB and LV, but this remains an experimental treatment.²⁶
• The combination of phenformin and ethylestrenol, which enhances endogenous blood fibrinolytic activity by increasing plasminogen activating enzymes, has been suggested as a treatment.
• Browning and Callen²⁷ reported that warfarin is a useful and effective treatment for LV associated with cryofibrinogenemia and hyperhomocysteinemia.
• Some reports have noted the use of heparin,²⁸ LMWH, psoralen plus ultraviolet A (PUVA), and low molecular weight dextran.
• If ulcers are superinfected, they should be treated with oral antibiotics.
• Meiss et al⁸ noted that hyperhomocysteinemia can be another cause of hypercoagulability and LV and that the combination of folic acid, vitamin B-12, and vitamin B-6 (cofactors of homocysteine metabolism) is an effective treatment for hyperhomocysteinemia, hypercoagulability, and LV.

Consultations

To fully evaluate for the comorbid conditions of LV, consult a hematologist (to evaluate for factors that lead to hypercoagulable states) and vascular surgeons (to evaluate and treat underlying defects of coagulation).

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Drugs stimulating endogenous fibrinolytic activity and drugs inhibiting thrombus formation (antiplatelet and anticoagulant) are possible treatments of LV.

Drug Category: Cardiovascular agents

These agents are the DOCs. They may be useful in reducing pain and ulceration.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Further Outpatient Care

• No specific care exists besides the medications previously mentioned for LV.

Complications

• LV can result in AB or white stellate scars.

Prognosis

• LV, although painful, is not associated with any loss of life or limb.

Patient Education

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

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

Medical/Legal Pitfalls

• Failure to perform a careful history and physical examination to rule out hypertensive ischemic ulcers, traumatic ulcers, and chronic periarteritis nodosa can result in an incorrect diagnosis and delay appropriate therapy.

ACKNOWLEDGMENTS

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• References

We gratefully acknowledge the contributions of Dr. Richard H. Musgnug, author of the previous edition of this article.

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Acknowledgments
• 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, Frezzolini A, Di Giulio S, De Matteis W, 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. 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, Hamulyak 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. Toth C, Trotter M, Clark A, Zochodne D. Mononeuropathy multiplex in association with livedoid vasculitis. Muscle Nerve. Nov 2003;28(5):634-9. [Medline].
16. Marzano AV, Vanotti M, Alessi E. Widespread livedoid vasculopathy. Acta Derm Venereol. 2003;83(6):457-60. [Medline].
17. Cardoso R, Gonçalo M, Tellechea O, Maia R, Borges C, Silva JA, et al. Livedoid vasculopathy and hypercoagulability in a patient with primary Sjögren's syndrome. Int J Dermatol. Apr 2007;46(4):431-4. [Medline].
18. Anavekar NS, Kelly R. Heterozygous prothrombin gene mutation associated with livedoid vasculopathy. Australas J Dermatol. May 2007;48(2):120-3. [Medline].
19. Ackerman AB, Chongchitnant N, Sanchez J. Histologic Diagnosis of Inflammatory Skin Diseases: An Algorithmic Method Based on Pattern Analysis. 2^nd ed. Baltimore, Md: Williams & Wilkins; 1997.
20. Sams WM. Livedo vasculitis. Therapy with pentoxifylline. Arch Dermatol. May 1988;124(5):684-7. [Medline].
21. 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].
22. 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].
23. 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].
24. Kern AB. Atrophie blanche. Report of two patients treated with aspirin and dipyridamole. J Am Acad Dermatol. Jun 1982;6(6):1048-53. [Medline].
25. Purcell SM, Hayes TJ. Nifedipine treatment of idiopathic atrophie blanche. J Am Acad Dermatol. May 1986;14(5 Pt 1):851-4. [Medline].
26. Amital H, Levy Y, Shoenfeld Y. Use of intravenous immunoglobulin in livedo vasculitis. Clin Exp Rheumatol. May-Jun 2000;18(3):404-6. [Medline].
27. Browning CE, Callen JP. Warfarin therapy for livedoid vasculopathy associated with cryofibrinogenemia and hyperhomocysteinemia. Arch Dermatol. Jan 2006;142(1):75-8. [Medline].
28. Heine KG, Davis GW. Idiopathic atrophie blanche: treatment with low-dose heparin. Arch Dermatol. Aug 1986;122(8):855-6. [Medline].
29. Bisalbutra P, Kullavanijaya P. Sulfasalazine in atrophie blanche. J Am Acad Dermatol. Feb 1993;28(2 Pt 1):275-6. [Medline].
30. Bollinger A. [White atrophy: skin infarction of various pathogeneses?]. Vasa. 1981;10(1):67-9. [Medline].
31. Bollinger A, Leu AJ. Evidence for microvascular thrombosis obtained by intravital fluorescence videomicroscopy. Vasa. 1991;20(3):252-5. [Medline].
32. 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].
33. 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].
34. Frances C, Barete S. Difficult management of livedoid vasculopathy. Arch Dermatol. Aug 2004;140(8):1011. [Medline].
35. Grattan CE, Burton JL. Antiphospholipid syndrome and cutaneous vasoocclusive disorders. Semin Dermatol. Sep 1991;10(3):152-9. [Medline].
36. Kluken N, Zabel M. [Pathologic anatomy of white atrophy]. Phlebologie. Jul-Sep 1986;39(3):561-6. [Medline].
37. 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].
38. 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].
39. Lewerenz V, Burchardt T, Buchau 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].
40. 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].
41. Millan G. Les atrophies cutane'es syphilitques. Bull Soc Fr Derm Syph. 1929;36:865-71.
42. Milstone LM, Braverman IM. PURPLE (oops! Atrophie blanche) revisited. Arch Dermatol. Dec 1998;134(12):1634. [Medline].
43. Pascarella L, Bergan JJ, Mekenas LV. Severe chronic venous insufficiency treated by foamed sclerosant. Ann Vasc Surg. Jan 2006;20(1):83-91. [Medline].
44. 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].
45. 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].
46. Shornick JK, Nicholes BK, Bergstresser PR, Gilliam JN. Idiopathic atrophie blanche. J Am Acad Dermatol. Jun 1983;8(6):792-8. [Medline].
47. Suarez SM, Paller AS. Atrophie blanche with onset in childhood. J Pediatr. Nov 1993;123(5):753-5. [Medline].
48. 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].
49. 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].
50. Vowden K. Lipodermatosclerosis and atrophie blanche. J Wound Care. Oct 1998;7(9):441-3. [Medline].

Article Last Updated: Mar 17, 2008