When A Patient Has A Painful Wound And Surrounding Purpura

A 30-year-old male presented to our wound clinic with a painful wound on his medial left ankle that had been present for approximately two years. Working as a cook, he was on his feet eight hours a day. He had surgery in the same area many years earlier as a child but did not have any complications from it.

A vascular surgeon saw him in the past for the same wound and had simply debrided the wound after performing imaging to rule out any underlying pathology. The vascular surgeon did not obtain a biopsy. The patient was only taking ibuprofen despite the intense pain and he was desperate for some kind of relief. His medical history was significant only for hypertension with the review of systems being unremarkable. The patient denied a history of smoking.

The physical exam revealed a dry necrotic eschar, approximately 3 cm in diameter, with surrounding purpura on the medial ankle that was exquisitely painful. Pedal pulses were palpable. There were no varicosities or edema. There was no exudate, odor, purulence or other signs of infection. X-rays ruled out underlying osteomyelitis or occult infection, and were unremarkable. Vitals were normal except for a slightly elevated blood pressure.

Due to the appearance and chronicity of the wound in an otherwise relatively healthy patient, my attending and I determined that he needed a biopsy. However, the patient wanted to wait until his next visit to do the biopsy. He wanted to take time off from work as he expected a painful recovery. At his next appointment two weeks later, using local anesthesia, we obtained a 4 mm punch biopsy of the lesion.

Key Questions To Consider

1. What is your diagnosis of this condition?
2. What are the key characteristics of this condition?
3. What are the positive findings on biopsy?
4. What are the treatment options?

Answering The Key Diagnostic Questions
1. Livedoid vasculopathy
2. This consists of painful stellate, purpuric vascular lesions that eventually ulcerate. This condition is worse in the summer.
3. Findings include hyalinized vascular changes of the subintimal layer of dermal blood vessels, endothelial proliferation, fibrin deposition and thrombosis.
4. Treatment options include anticoagulants, immunoglobulin, immunosuppressive therapy, anti-inflammatories, psoralen plus ultraviolet light therapy (PUVA), danazol and hyperbaric oxygen therapy.

What You Should Know About Livedoid Vasculopathy
The biopsy report came back as livedoid vasculopathy and we made a referral to vascular surgeons for their input on the wound and advice on treating this vascular lesion. They only recommended serial debridement, which required local anesthesia each time due to intense pain. Despite a hospital admission at week six for antibiotic treatment of cellulitis, the patient healed by week eight with no more pain and was fully functional.

Livedoid vasculopathy is a disorder, almost exclusively of the lower extremities, that consists of intensely painful stellate vascular lesions that eventually ulcerate. Feldaker first reported it in the 1950s, identifying the condition as a coagulation disorder and naming it “livedo reticularis with summer ulceration.”¹ Other terms have emerged for the condition with clinicians referring to livedoid vasculopathy as segmental hyalinizing vasculitis, painful purpuric ulcers with reticular pattern of the lower extremities (PPURPLE) and atrophie blanche.

The etiology is unclear but livedoid vasculopathy can be associated with various clotting disorders and autoimmune diseases like systemic lupus erythematosus and scleroderma.² Frequently, however, it is idiopathic. Its association with hypercoagulable states like factor V Leiden makes the most sense as researchers have shown that livedoid vasculopathy is a recurrent thrombosis of the cutaneous microcirculation.³ This recurrent thrombosis produces cutaneous ischemia, which eventually results in necrosis and ultimately ulceration. Thankfully, this condition is quite rare with an incidence of 1:100,000. It mostly occurs in young women ranging from 15 to 30 years of age.^1,3 Like its first given name states, this disease does seem to have summer exacerbations and winter remissions.^3,4

Essential Diagnostic Insights
The patient with livedoid vasculopathy will present with painful purpuric ulcerations almost exclusively of the lower extremities. This includes the distal lower leg, ankles and back of the feet.^3-5 In regard to the intense pain due to ischemia, Drabik and colleagues called this ischemia angina cutis.³ One may notice lacy red streaks that are similar to livedoid vasculopathy. Livedoid vasculopathy causes permanent damage, leaving behind scar tissue and atrophie blanche.^3,4 Lab tests and imaging are not particularly useful as most are normal or unremarkable for this condition. While these patients have pedal pulses and an ankle/brachial index will be normal, researchers have documented reduced transcutaneous oximetry measurements in many patients with livedoid vasculopathy.⁵

The most helpful diagnostic tool is the biopsy. This will possibly show multiple things, including hyalinized/vascular changes of the subintimal layer of dermal blood vessels, endothelial proliferation, fibrin deposition and thrombosis.^2-5 However, the biopsy will most likely not show an inflammatory infiltrate.³

Pertinent Pearls On Treatment    
Unfortunately, there is no gold standard for treating livedoid vasculitis, likely owing to the rarity of the condition. Accordingly, the literature regarding treatment of this condition is also lacking with high quality studies being few and far between. There have been many suggested treatments including anticoagulants, immunoglobulin, immunosuppressive therapies (including steroids), anti-inflammatories, psoralen plus ultraviolet light therapy, danazol and even hyperbaric oxygen therapy. However, there has been minimal testing and no extensive study of these modalities.

For example, it makes sense that with livedoid vasculitis being a thrombotic condition, anticoagulation would be the first-line therapy. Indeed, a widely accepted treatment in Europe is daily subcutaneous injections of 1-2 mg/kg of enoxaparin sodium (Lovenox, Sanofi) until resolution.^1,3 Multiple authors of small case studies have claimed improvement with heparin, low-molecular-weight heparin and low-dose warfarin (Coumadin, Bristol-Myers Squibb), but large prospective studies are scarce.^6-9 Currently, Drabik and colleagues are conducting a phase II therapeutic, multicenter prospective trial on the use of rivaroxaban (Xarelto, Janssen Pharmaceuticals) in the treatment of livedoid vasculopathy, but the study only involves 20 patients.³ Perhaps the results of this study will lead to larger trials in the future but for now, treatment with anticoagulation is still off-label.

Another promising treatment of livedoid vasculopathy is via immunoglobulins. Monshi and coworkers in 2014 did a 10-year follow-up on 11 consecutive patients with livedoid vasculopathy treated with IV immunoglobulins.¹⁰ There were a total of 29 disease episodes, all of which the treating physicians treated with high-dose IV immunoglobulin (2 g/kg every four weeks for an average of six months). After the first IV immunoglobulin cycle, there was an overall 50 percent reduction in pain with that number increasing to 80 percent after the second cycle. Patients achieved remission in 59 percent of disease episodes after three cycles, 86 percent after six cycles and 93 percent after eight cycles. Side effects were minimal with some nausea and vomiting that resolved after slower administration. Other authors have shown the same positive effects but larger high-quality studies must confirm this.²

Hyperbaric oxygen therapy (HBOT) is a logical treatment modality considering the ischemic nature of the disease but again, the literature is lacking. One study by Juan and colleagues in 2006 focused on 12 patients with ulceration due to livedoid vasculopathy who were treated with five sessions of HBOT a week.¹¹ Only eight patients completed the study but ulcerations healed in an average of 3.4 weeks for those patients. By the fourth or fifth session, patients were all walking with significantly reduced pain. Six of the patients had a relapse but all responded to another course of HBOT. Banham noted the same positive effects of HBOT on livedoid vasculopathy in a small case study in 2013.⁵ However, larger high-quality studies are necessary to confirm the efficacy of HBOT to justify its use for livedoid vasculopathy.⁵

In Conclusion
As this disease occurs almost exclusively in the lower extremity, podiatric physicians should consider livedoid vasculopathy any time a patient presents with a painful purpuric ulceration, particularly if the patient is a young, healthy woman. 

Dr. Vella is in private practice in Gilbert, Ariz.

References

1. Kerk N, Goerge T. Livedoid vasculopathy--current aspects of diagnosis and treatment of cutaneous infarction. J Dtsch Dermatol Ges. 2013; 11(5):407-410.
2. 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):1135-1139.
3. Drabik A, Hillgruber C, Goerge T. A phase II multicenter trial with rivaroxaban in the treatment of livedoid vasculopathy assessing pain on a Visual Analog Scale. JMIR Res Protoc. 2014; 3(4):1-10.
4. Feng S, Su W, Jin P, Shao C. Livedoid vasculopathy: clinical features and treatment in 24 Chinese patients. Acta Derm Venereol. 2014; 94(5):574-78.
5. Banham NDG. Livedoid vasculopathy successfully treated with hyperbaric oxygen. Diving Hyperbar Med. 2013; 43(1):35-36.
6. Becker A, Stoffels-Weindorf M, Schimming T, Dissemond J. Recurrent leg ulcers due to livedoid vasculopathy: successful treatment with low-molecular-weight heparin. Dtsch Med Wochenschr. 2013; 138(28-29):1458-62.
7. 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.
8. 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.
9. Kavala M, Kocaturk E, Zindanci I, et al. A case of livedoid vasculopathy associated with factor V Leiden mutation: successful treatment with oral warfarin. J Dermatolog Treat. 2008; 19(2):121-3.
10. Monshi B, Posch C, Vujic I, et al. Efficacy of intravenous immunoglobulins in livedoid vasculopathy: Long-term follow-up of 11 patients. J Am Acad Dermatol. 2014; 71(4):738-44.
11. Juan WH, Chan YS, Lee JC, et al. Livedoid vasculopathy: long-term follow-up results following hyperbaric oxygen therapy. Br J Dermatol. 2006; 154(2):251-55.