Surgical Management of Lower Extremity Pyoderma Gangrenosum With Viable Cryopreserved Umbilical Tissue

A Case Series

Robert Fridman, DPM, FACFAS, CWSP; Tzvi Bar-David, DPM, FACFAS; Joseph Larsen, DPM, FACFAS; Andrew R. Olson, DPM

Disclosures

Wounds. 2020;32(4):101-106. 

In This Article

Abstract and Introduction

Abstract

Introduction: Pyoderma gangrenosum (PG) is a rare skin disease that often presents as a uniquely painful and necrotic ulceration of the lower extremity. Pyoderma gangrenosum is often misdiagnosed and can have deleterious consequences to the patient, as there is no gold standard treatment and it can be difficult to manage. Surgery for these wounds is controversial, as pathergy can develop, worsening the ulceration. Advanced wound care products such as cellular- and/or tissue-based products (CTPs) are effective in helping stagnant chronic wounds reach full closure. Amnion/chorion-based skin substitutes that have been cryopreserved and contain viable cells have been shown to promote more cell recruitment and reduce inflammation.

Objective: This case series presents evidence of using a cryopreserved umbilical cord tissue with living cells in adjunctive treatment of wounds associated with PG.

Materials and Methods: This report presents 3 different clinical scenarios of lower extremity PG treated surgically with viable cryopreserved umbilical tissue (vCUT).

Results: All 3 patients were successfully treated with vCUT and resulted in complete healing.

Conclusions: To the best of the authors' knowledge, this is the first case series demonstrating the ability of vCUT to heal these difficult-to-treat ulcers. In addition, it may be an effective modality to adjunctive management of PG.

Introduction

Pyoderma gangrenosum (PG) is a rare skin disease that often presents as a uniquely painful and necrotic ulceration of the lower extremity. Histologically, it is characterized by an increased number of neutrophils in the dermis in the absence of infection.[1,2] About half of PG cases are associated with systemic diseases, such as inflammatory bowel disease, polyarthritis, and hematologic disorders.[3] The pathogenesis of PG remains poorly understood, but it is thought to be a multifactorial combination of neutrophil dysfunction, inflammatory mediators, and genetic predisposition.[4] This supports the theory that PG is a hyperreactive response to inflammation and trauma in predisposed patients.[5] Currently, there are no specific lab tests or histopathologic exams to confirm PG, and it is usually a diagnosis of exclusion.[6] As many as 10% of PG cases may be misdiagnosed, with mimickers including vascular occlusive disease or venous disease, vasculitis, cancer, primary infection, necrotizing fasciitis, exogenous tissue injury, or other inflammatory diseases.[5] The misdiagnosis of PG can have grave consequences, because treatment intended for PG with high-dose prednisone or immunosuppressive medications may be contraindicated in patients with diseases that may produce ulceration-mimicking PG, such as an infectious or malignant process.[7]

There is no gold standard treatment for PG, and it can be difficult to manage.[8–10] The management goals are to control local and systemic inflammation and improve wound healing. Most treatment regimens involve both topical and systemic immunosuppressants with appropriate wound care and pain management.[11] Commonly used agents include systemic corticosteroids, cyclosporine, infliximab, and canakinumab, primarily targeting the inflammatory response.[12] Recently, tumor necrosis factor alpha inhibitors have been used for refractory PG.[8,13,14] Initial improvement of ulcers may occur within days of starting treatment, but complete ulcer healing often requires weeks to months.[8,13,14] Therefore, there remains a high rate of nonresponse and recurrence.

Surgical management of PG ulcers is divisive, with 25% to 50% of these cases potentially exhibiting pathergy in which a minor trauma can lead to the development of ulcers that may be resistant to healing.[15] Pyoderma gangrenosum ulcers can be aggravated by surgery, which is often a hallmark when considering the diagnosis of PG. Pathergy may be mediated by ensuring the patient's PG is clinically dormant prior to surgery.[16,17] Select literature supports surgical intervention in conjunction with medical management in the forms of free-flaps, split-thickness skin grafts, and cultured keratinocyte autografts.[18–20]

Advanced wound care products such as cellular- and/or tissue-based products are effective in helping stagnant chronic wounds reach full closure. The benefits of using human placental tissues in tissue regeneration are now well documented.[21,22] Optimally preserved placental membranes are of particular interest, as they contain a combination of growth factors and extracellular matrices as well as viable mesenchymal stem cells, fibroblasts, and epithelial cells. These components have been shown to decrease inflammation,[23] lower microbial loads,[24] and promote tissue regeneration.[25] Furthermore, amnion/chorion-based skin substitutes that have been cryopreserved and contain viable cells have been shown to promote more cell recruitment and reduce inflammation better than devitalized placental membranes.[26,27] This consecutive case series presents evidence of using a cryopreserved umbilical cord tissue with living cells in treating patients diagnosed with PG.

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