Successful healing of a chronic ulcer in livedoid vasculopathy using PuraPly: A case report

Introduction

Livedoid vasculopathy (LV) is a rare thrombotic vasculopathy of the dermis that is characterized by painful, often reoccurring, ulcers on the lower extremities. The treatment course of LV is challenging as it is poorly defined and understood.¹ A higher incidence of LV is associated with certain conditions, behavioral factors, and other social determinants of health. These include hypercoagulable states, connective tissue diseases, venous stasis, smoking, and care inaccessibility.² The pathophysiologic mechanism of LV is not completely understood. However, the current understanding shows LV as a vascular disease dominated by procoagulation factors which leads to hypercoagulability. This may occur due to epithelial dysfunction increasing fibrin formation or restricting fibrinolysis.² This fibrin deposition and decreased vascular persuasion, and therefore decreased oxygen supply to the tissues, leads to tissue necrosis.

LV remains a chronic condition with treatment goals including resolution or improvement of skin lesions, prevention of recurrence, and reduction of pain and debilitation. Current treatment options include nonsteroidal anti-inflammatory drugs, antiplatelet agents, fibrinolytics, vasodilators, and direct oral anticoagulants but efficacy remains variable with risk of adverse events– particularly in patients with comorbidities. While treatment guidelines for LV exist– such as those outlined in the Delphi consensus and AWMF S1-Guideline– they emphasize anticoagulation and systemic therapies, which were not feasible in this case due to the patient’s elevated bleeding risk. The management of LV remains challenging, particularly when standard pharmacologic options are contraindicated or poorly tolerated.³

We present the case of a patient with a chronic LV wound that healed successfully following serial application of PuraPly, after nearly a year of unsuccessful traditional wound care with little to no significant improvement. This case underscores the need for adaptable treatment strategies that can be tailored to individual patient factors and highlights the potential role of advanced wound care modalities such as PuraPly. This case demonstrates a safe, effective, and localized treatment option in a patient who was unable to tolerate traditional, systemic pharmacologic agents due to bleeding risk. This highlights the role of PuraPly in advanced wound care to promote tissue regeneration as an adjunctive or monotherapeutic option for patients with LV.

Case report

A 69 years old female presented to the dermatology clinic with a malodorous, nonhealing wound located on the right ankle (Fig 1). The patient reported having the ulcer for approximately 1 year during which time she was receiving weekly treatments at a rural wound clinic before being referred to Dermatology. Despite ongoing treatments, the patient reported no improvement and possibly worsening of the wound with a significant toll on her quality of life and threat to her job which consisted of mostly standing.

Fig 1.

Patient presented initially with nonhealing wound on right medial ankle (A and B).

A diagnostic work up was executed including a 3 mm punch biopsy and wound culture swab. The culture reported the presence of Staphylococcus aureus. The histopathology report described prominent fibrin deposition in small-caliber dermal vessels with associated fibrosis and ulceration, consistent with features of atrophie blanche (LV), despite the absence of frank thrombi or vasculitis (Fig 2). No evidence of atypia was observed. A full systematic diagnostic work-up for conditions associated with LV– such as thrombophilias (hereditary or acquired), connective tissue disease, paraproteinemias, and vascular insufficiencies– was not performed at the time of evaluation due to access limitations and bleeding risk concerns. However, the patient, age 69, has no personal or family history of thrombotic events, autoimmune disease, or hematologic disorders. She denied systemic symptoms such as joint pain, Raynaud’s, or neurologic changes and her exam revealed no edema or signs of peripheral arterial disease. Venulectasias were noted, but distal pulses were intact. Given the patient’s age, stable health history, and limited access to subspecialty testing, the likelihood of an undiagnosed systemic condition driving the ulcer appeared low. The patient was diagnosed with LV with ulceration and Atrophie Blanche distributed on the right distal pretibial region.

Fig 2.

Punch biopsy of the right medial ankle. Tissue stained with hematoxylin and eosin stain.

Since the patient was a heavy smoker, there was concern about initiating a medication which could increase risk of a gastrointestinal bleed. The patient was started on pentoxifylline 400 mg 3 times a day as tolerated, cephalexin 500 mg 4 times daily as tolerated, as well as mupirocin 2% topical ointment, applied to the affected area 2-3 times daily. The patient was also counseled on the importance of smoking cessation.

Left (Magnification ×100): Original magnification demonstrating epidermal ulceration and underlying dermal fibrosis. Right (Magnification ×200): higher magnification of the dermis highlighting prominent fibrin thrombi within small-caliber vessels.

Two weeks after initial workup, the patient reported an inability to tolerate pentoxifylline due to flaring of their gastroesophageal reflux disease. The treatment was adjusted to 81 mg of aspirin twice a day as tolerated and prescribed amoxicillin 875 mg-potassium clavulanate 125 mg once daily for 2 weeks. The pentoxifylline was discontinued. The wound minimally improved with continued debilitating pain, difficulty walking, and persistent malodorous wound exudate. The patient went on medical leave as she was no longer able to walk long distances or stand for long periods at her job.

One month later, the patient returned to the clinic and reported they were hospitalized due to a ruptured gastric ulcer and aspirin was discontinued. The patient was counseled on the importance of smoking cessation and avoidance of all medications which could increase bleeding risk despite their role in LV management. Of note, the patient quit smoking at this time. At this point, we introduced a trial of PuraPly application to the wound with no oral pharmacologic therapy. PuraPly Antimicrobial Wound Matrix is a cross-linked extracellular matrix scaffolding which consists of a collagen sheet coated in 0.1% polyhexamethylene biguanide hydrochloride.

The wound was cleansed with Hibiclens, debrided, and rinsed with sterilized water. The PuraPly AM was handled using aseptic technique and was cut to size of the wound bed. The matrix was secured using a nonadherent pad, Steri-Strips, and subsequently wrapped with Coban dressing. Although Coban dressing is commonly used for compression therapy in venous ulcers, in this case, the dressing was employed solely to secure the wound dressing and manage local edema. The patient’s clinical evaluation did not suggest chronic venous insufficiency, and no venous reflux studies were performed. The patient was instructed not to remove the PuraPly matrix and to keep the bandaged area dry until removal. The patient was scheduled for weekly follow-up for wound assessment and reapplication of the PuraPly AM until resolution of the wound. This regimen continued for 9 continuous cycles (10 once weekly dressing matrix applications total), resulting in significant improvement and eventual resolution of the wound.

The patient adhered to regular follow ups. Upon healing, the lesion site demonstrated stellate hypopigmented scarring with faint surrounding erythema, consistent with atrophie blanche (Fig 3, G), further supporting the clinical diagnosis of LV. Despite a recurrence of the ulcer 3 months after the initial wound had completely healed, the wound was fully healed again using monotherapeutic weekly PuraPly application for 2 months and has remained stable without further complications for 14 months since. She was able to return to her job and stand for extended periods of time. This highlights the sustained efficacy of the bandage wound matrix and treatment plan.

Fig 3.

Wound presentation at initial dressing application, first cycle (A). Wound Presentation after third cycle (B). Wound after fifth cycle (C). Wound after seventh cycle (D). Wound after ninth cycle (E). Wound considered healed, 1 week follow up after last matrix application (F). Wound 13 months after wound was considered healed. (G).

Discussion

The treatment of LV can be challenging for providers due to an unclear treatment course and chronic nature typically affecting patients with pre-existing comorbidities. LV negatively affects individuals physically, psychologically, and, in some cases, socioeconomically if the ulcer is so severe it prevents the individual from working, as in this case. These ulcers may demonstrate delayed healing due to factors such as advanced age, endothelial cell injury, intrinsic hypercoagulability, larger wound area, and other social behaviors.³ Microbial resistance and biofilms have also been shown to impair healing and lead to wound infection. Studies have shown that most chronic wounds are likely to develop biofilm.⁴ Patients are often cycled through multiple systemic antibiotics, increasing risk of resistance and disruption of the gut microbiome. Healing of the wound typically takes anywhere from 4 weeks to over 6 months depending on the size and other factors, and often recur. Due to their complexity, the multiple factors affecting the healing of these ulcers, and the large negative impacts felt by the patient, healing these ulcers is typically a difficult and slow achievement. Lasting, effective, well-tolerated treatments remain an important area of research.

PuraPly AM is approved for various types of wounds such as pressure ulcers, venous ulcers, chronic vascular ulcers, surgical wounds, and more. Debridement before the placement of PuraPly AM allows for the removal of surface biofilm. The biofilm must then be targeted using a broad-spectrum antimicrobial agent. PuraPly AM uses polyhexamethylene biguanide hydrochloride and 2 layers of collagen which are cross linked to resist proteolytic depredation and enhance a sustained antimicrobial effect to kill wound microbes and destroy biofilm as well as prevent regrowth with no known antibiotic resistance or cytotoxicity in host cells.⁴ As the wound’s healing progresses, the collagen framework allows fibroblasts to migrate with greater facility to close the wound.

The absence of a comprehensive laboratory or vascular work-up represents a limitation of this case. However, the patient’s age, lack of systemic symptoms, and negative personal and family history made an underlying systemic etiology less likely.

Overall, LV is a painful and oftentimes debilitating condition. Due to the patient’s inability to tolerate standard first line medications, the PuraPly AM treatment method was implemented. In only 13 weeks, this method was able to heal the burdensome ulcer which had been present for almost a year despite attempted therapy. This report highlights the challenges associated with treatment of LV and may offer guidance for providers managing LV in patients with contraindications to systemic therapy. Based on the aforementioned case, we feel that PuraPly should be further considered and researched as an adjuvant or, when necessary, monotherapeutic treatment option in patients with LV.

Conflicts of interest

None disclosed.