Utility of a Synthetic Hybrid-Scale Fiber Matrix in the Management of Pyoderma Gangrenosum: A Case Study

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PG is a rare, inflammatory skin condition that initially presents as papules but later progresses to large, painful ulcers. This skin condition was first described by Brocq and Simon¹ in 1908 and is classified as a neutrophilic dermatosis. Although PG is considered idiopathic, it is associated with systemic diseases in approximately 50% of cases.² These systemic diseases include hematologic diseases (eg, immunoglobulin A monoclonal gammopathy), rheumatologic disease (eg, rheumatoid arthritis and seronegative spondylarthritis),³ and, most commonly, inflammatory bowel disease (eg, primary ulcerative colitis).^3,4 PG is extremely painful and can be debilitating, with a mortality rate of 16% at 8 years and a threefold risk of death compared with the general population.⁵

The diagnosis of PG often is delayed or missed entirely.⁶ PG is considered a diagnosis of exclusion; however, an intralesional biopsy demonstrating neutrophilic infiltration confirms the diagnosis. Laboratory tests are useful to rule out other differential diagnoses such as infection, vasculitis, and/or autoimmune disorders.

PG is frequently found at sites exposed to accidental trauma. Most commonly, PG is seen on the lower extremities, mainly involving the pretibial skin.⁷ Cases of PG in other anatomic areas, including the abdominal wall and spine, typically are iatrogenic following surgery.^8,9 PG initially manifests as small papules that rapidly progress to painful, undermining, violaceous, necrotizing ulcerations with exudate.⁶ Typically, the pain caused by these lesions is out of proportion to that of the lesion.

The pathogenesis of PG is multifactorial. The first mechanism involves abnormal production of inflammatory cytokines. Elevated serum levels and expansion of T cells along the wound margins result in abnormal production of proinflammatory and chemotactic cytokines. These cytokines evolve into an "inflammasome" that becomes activated in environments of stress and infection. The second mechanism is a result of a genetic mutation in Janus kinase, which is a signal activator and transducer of the transcription pathway, resulting in neutrophil recruitment and proliferation as well as inflammation.¹⁰

PG has 2 distinct stages, an active stage and a healing stage, based on a patient’s signs and symptoms. In the active stage, lesions manifest with a halo-like, violaceous, and edematous appearance with undermining and rapidly expanding wound edges. Wounds in the active stage are extremely sensitive to pathergy, with minor trauma to the area resulting in a worsening of the condition and/or necrosis.² Pathergy is the hallmark of PG because it occurs with only 1 other rare disease, Behҫet disease, more commonly known as Silk Road disease. Patients in the active stage of PG may experience symptoms such as fever and/or malaise. Wounds in the healing stage demonstrate epithelial projections from the margins of the wound into the wound bed and so-called skin islands.

PG is extremely difficult to treat due to its multifactorial pathogenesis, association with systemic diseases, and wound pathergy. There is currently no standard treatment for PG. Most commonly, management consists of immunomodulatory pharmacological drugs, such as high-dose corticosteroids, tacrolimus, cyclosporine, and anti-TNF-α, along with nontraumatic local wound care.¹¹ While pharmacotherapy has been successful in managing PG progression and recurrence, there has been minimal advancement in the management of existing lesions.¹² Local wound care has been emphasized in an attempt to create and maintain a healthy and clean wound while minimizing exudate and maintaining the integrity of peripheral skin.¹³ Repetitive local debridement of these wounds is not recommended due to the tendency for pathergy.⁶ Proper choice of dressing or dressings can potentially improve both the size and symptoms of the wound. Synthetic grafts are emerging as adjuvant therapy due to their ability to mimic host tissue while also being biologically inert.¹² This technology is potentially advantageous for the management of PG in providing a wound matrix that bypasses pathergy.

The current case study used SHSFM (Restrata Wound Matrix; Acera Surgical Inc) in the management of recalcitrant PG ulcers of the lower extremity.

A 53-year-old female presented to the emergency department with a 3-week history of pruritic skin lesions along the dorsum of the left foot (Figure 1). Her past medical history is currently remarkable for poorly controlled hypertension (on lisinopril and hydrochlorothiazide), peripheral vascular disease, obesity, and 30-pack-year nicotine dependence. The family history was remarkable for colon cancer.

On initial presentation, the patient related that she noticed a lesion after "being bitten by something while walking barefoot in the yard." She admitted to "picking at" the lesion and expressing purulence, followed by self-treatment with bleach and topical triple antibiotic ointment. Radiographs demonstrated no obvious osseous abnormalities. The patient was discharged with a prescription for oral antibiotics and a referral to outpatient podiatry care.

On initial presentation to the wound care center, a full-thickness wound overlying the dorsolateral aspect of the foot was observed. The wound was composed of 75% fibrotic tissue and 25% black eschar. The periwound skin demonstrated mild erythema and mottling. No signs of infection were present. The wound was dressed with betadine-soaked gauze, and the patient was referred to the advanced wound care center for more specialized treatment. The patient was treated for approximately 10 months with local wound care modalities, including various dressings and biologic skin substitute grafts. Although PG was initially considered, biopsies were inconclusive, with "fibrotic tissue with marked necrosis and acute inflammation" reported. At times, the wound had positive cultures for methicillin-resistant Staphylococcus aureus, and the patient was treated accordingly with antibiotics.

During the course of treatment, the patient underwent multiple hospitalizations for various issues, including nausea and vomiting, lower extremity edema, melena, and painful draining wounds. While the patient was hospitalized, referrals were made to specialists in vascular surgery, infectious diseases, internal medicine, and gastroenterology. Extensive workup was conducted, with a summary of findings including a normal angiogram, normal rheumatoid panel, and normal hemophilia panel. Colonoscopy revealed reactive gastritis. PG was again considered, and a dermatologist was consulted. Punch biopsy results vaguely correlated to the diagnosis of PG. Hematoxylin-eosin staining showed ulcerated epidermis and dermis with associated neutrophils, lymphocytes, and histiocytes. Surrounding vessels were involved by neutrophilic and lymphocytic inflammation. These findings are altogether nonspecific but may represent PG. Dermatology-specific laboratory tests revealed an MTHFR mutation. A dermatologist started treatment with dapsone, prednisone, and infliximab infusions.

Local wound care therapy was modified after the proper diagnosis of PG was made. The patient was taken to the operating room, where light debridement was performed with a sterile chlorhexidine gluconate scrub brush, and the SHSFM was applied. The wound began to diminish in size. A second matrix was applied in similar fashion approximately 2 months later. Wound resolution was achieved after application of the SHSFM (Figure 2).

The patient developed a second wound on the lateral aspect of her left ankle (Figure 3). The SHSFM was used in the management of this wound as well. Six months postoperatively, the wound had significantly improved and there was near-complete resolution after a single application of the SHSFM (Figure 4).

Considerable debate remains regarding optimal management of PG. McPhie and Kirchhof ¹⁴ demonstrated that advanced immunomodulating drugs that target interleukin 17 and TNF in combination with local wound care resolved PG. However, other researchers have demonstrated paradoxical induction of PG when patients are placed on these inhibitors.^15,16

The debate concerning optimal treatment extends to synthetic vs biologic agents. Araújo et al¹⁷ published a case report demonstrating complete healing of a PG wound with combination therapy of immunosuppression drugs, autologous skin grafting, and hyperbaric oxygen therapy. However, they recommended not performing skin grafting during the active state because both donor and recipient site rejection can occur due to pathergy. Strunck et al¹⁸ determined that antimicrobial and superabsorbent dressings are beneficial because they require less frequent dressing changes and manipulation, ultimately limiting pathergy.

The current study demonstrates the successful use of an SHSFM in a single patient with recalcitrant lower extremity PG. Wound 1 epithelialized approximately 3 months after a second matrix application, whereas wound 2 achieved epithelialization after 1 matrix application.

Synthetic skin grafts have become increasingly popular due to their low antigenicity, biodegradability, toxicity, risk of chronic inflammatory response, and recipient rejection.¹⁹ SHSFM is a fully synthetic, nanofabricated scaffold with high porosity similar to native extracellular membrane.¹⁶ It is composed of polyglactin 910 and polydioxanone, which are electrospun into a hybrid-scale porous matrix that promotes fibroblast proliferation, collagen upregulation, and neovascularization, and prevents bacterial penetration.²⁰

This study has limitations. First, it is a retrospective case study of a single patient, so the authors cannot state that these results are reproducible. Second, in conjunction with SHSFM application, the patient was also treated with local wound debridement and dermatologic medications; thus, it cannot be concluded that SHSFM alone healed the patient’s wounds. Finally, the patient in this report was not directly compared with any control or adjunctive therapy groups.

To the authors' knowledge, this is the first study advocating the use of SHSFM as a primary treatment option for PG. This study demonstrates the success of SHSFM in the management of recalcitrant PG in 1 patient. The authors suggest that the success in accelerating PG wound healing in this case is due to SHSFM mimicking human extracellular membrane and providing a porous scaffold for cellular ingrowth and angiogenesis. SHSFM is also beneficial because it minimizes host reactivity and inflammatory response, ultimately reducing the risk of pathergy. Use of an SHSFM is a promising strategy for the management of refractory PG wounds. A large, retrospective, or prospective cohort treated in a similar fashion is needed to further elucidate the validity of the current study.

Authors: Kaitlyn J. Loesel, DPM; Blake E. Pritchett, DPM; Alexander Schultz, DPM; and Jonathan M. Towarnicki, DPM

Affiliations: Podiatric Medicine and Surgery, Department of Orthopedics, University of Louisville, Louisville, KY

ORCID: Loesel, 0009-0001-0563-2184; Pritchett, 0009-0009-7132-2596; Schultz, 0000-0002-2421-0593; Towarnicki, 0009-0005-7513-1253

Disclosure: The authors disclose no financial or other conflicts of interest.

Correspondence: Kaitlyn Loesel, DPM; Resident Physician, University of Louisville, Department of Orthopedics, 530 S Jackson St, Louisville, KY 40202; kaitlyn.Loesel@uoflhealth.org

Manuscript Accepted: July 31, 2024