Complex Wound Reconstruction in a Patient With Ehlers-Danlos Syndrome

Summary:

Ehlers-Danlos syndrome (EDS) is a hereditary condition marked by collagen defects leading to tissue fragility throughout various body systems. One notable challenge for patients with EDS is compromised wound healing due to connective tissue fragility. This study described the case of a 53-year-old man with classical type EDS, presenting with a significant wound over his left knee, following numerous complications after a patellar tendon rupture. Traditional healing methods, including a gastrocnemius flap, were of limited benefit due to the patient’s EDS condition. A novel surgical approach, involving the use of a split-thickness skin graft combined with the Recell Autologous Skin Cell Harvesting Device, resulted in successful wound healing. Ten months postsurgery, the patient demonstrated excellent graft adherence without any complications. This case indicates the potential benefits of the split-thickness skin graft and Recell method for patients with EDS, offering an effective treatment modality for significant wound healing challenges in this population.

Ehlers-Danlos syndrome (EDS) is a heritable collagen-defect disorder that renders soft tissues, vessels, and organs fragile, increasing morbidity and mortality.¹ Fourteen clinical types caused by 19 genes are recognized.²

Classical EDS (cEDS) features joint hypermobility; markedly elastic, friable skin; and poor wound healing complications. Dermal thinning results in extensive trauma from typically low-level impacts and/or sheering forces causing large avulsions known as Morel–Lavallee lesions.²

Connective tissue fragility compromises normal repair, leading to wound dehiscence, bleeding, and chronic wounds.³ Injuries and lesions in patients with EDS need extensive repair using complex closure techniques due to dermal structure retraction and limited subdermal structure adherence.^1,3–5

Given limited literature on successful wound closure in cEDS patients, the case herein describes an EDS patient who developed a large wound overlying a joint, which was successfully healed by applying a split-thickness skin graft (STSG) and the Recell Autologous Skin Cell Harvesting Device (Recell, Avita Medical, Valencia, CA), a mechanochemical system that processes a small skin sample into an autologous cell suspension used to spray over a large surface. The patient’s skin remains intact with no complications at 10-month follow-up.

CASE PRESENTATION

A 53-year-old man with cEDS ruptured his left patellar tendon following a mechanical fall. The postoperative course was complicated by methicillin-susceptible Staphylococcus aureus necrotizing fasciitis and osteomyelitis, necessitating extensive debridement down to bone and subsequent coverage with a medial gastrocnemius muscle flap. Case chronology can be seen in Figure 1.

Fig. 1.

Timeline.

The patient was a nonsmoker with a history of complex cardiac disease and a patellar tendon rupture, who presented with a complex wound over his left knee at the site of the patellar tendon repair and muscle flap with skin coverage.

He initially underwent a left patellar tendon repair. On postoperative day 4, he developed a septic joint and necrotizing fasciitis, requiring urgent serial debridement of joint and soft tissue, and intravenous antibiotics. After infection control, he underwent patellar tendon reconstruction with a left medial gastrocnemius flap for joint coverage and overlying bilayered dermal substitute Integra (Integra LifeSciences Corp., Plainsboro, NJ), negative-pressure wound therapy, and an external fixator. Integra protected the gastrocnemius flap in the weeks before skin grafting.

To enhance collagen synthesis, angiogenesis, and oxygen delivery, a multidisciplinary regenerative medicine team added injections of 100 mg testosterone enanthate biweekly, 0.2 mg human growth hormone daily, and 6 weeks of outpatient hyperbaric oxygen treatment. These modalities have shown benefit in difficult‑to‑heal wounds and were well tolerated. He was referred to the burn team for definitive coverage.

The anterior‑knee defect measured 22 × 18 cm with overlying Integra covering the medial gastrocnemius flap. There were noticeable atrophic, hyperpigmented scars across the lower extremity (Fig. 2). It was determined that the patient would benefit from an STSG with the Recell Autologous Skin Cell Harvesting Device over the meshed autograft.

Fig. 2.

Preoperative wound measuring 22 × 18 cm.

OPERATIVE PROCESS

After excisional preparation, an STSG was harvested at 0.008ʺ depth and meshed 3:1 (≈396 cm²). After securing the autograft, an 8 × 1 cm portion was processed for keratinocyte suspension using Recell, enabling the production of spray-on skin cells. The reconstituted solution was prepared into syringes for aerosolization with an approximate expansion of 80:1 to resurface the autografted left knee and donor site. The spray-on skin cells were applied with a nonstick cover and surgical dressing placed over the left knee and poly-L-lactic acid (Suprathel) synthetic skin substitute, nonstick cover, and surgical dressing placed over the donor site. The total volume of the keratinocyte suspension measured 7.5 cc to cover 600 cm² for the recipient and donor sites.

On postoperative day 7, evaluation demonstrated adherence of the STSG with no signs of infection. Follow-up visits revealed continued STSG take and 99% graft adherence along the wound bed at 2 weeks, 2 months (Fig. 3), and 39 months (Fig. 4). The donor site was fully healed with minimal scarring.

Fig. 3.

follow-up wound evaluation—10 months.

Fig. 4.

follow-up wound evaluation—39 months.

FOLLOW-UP AND OUTCOMES

At 14-month follow-up, most normal functionality was regained, including walking, scaling stairs, and exercising. Despite sunscreen use, the graft became hyperpigmented, expected in patients with EDS.

DISCUSSION

Complex wounds necessitate a multistage approach, incorporating various products to prime the wound bed and optimize healing. In patients with underlying healing pathologies, surgical techniques require sophistication to achieve final closure without tissue breakdown. In our patient, we primed the wound bed with the dermal substitute Integra after a clean wound was established. This first step in reconstruction allowed for a robust foundation to apply the autograft. Due to compromised cutaneous healing secondary to the hyperelasticity and narrowing of dermis in cEDS, a thinner confluent sheet of skin was obtained than would normally be harvested for an STSG, allowing better donor site healing. To fill the interstices of the meshed autograft and reduce donor skin, Recell was used overtop the recipient and donor sites.

Wound bed priming and donor skin optimization contributed to successful healing and closure of this large wound. This remains among the few cases described of successful skin grafting in individuals with EDS, and the only case, to the knowledge of the team, using Recell in the operative process and successful grafting of a large meshed 3:1 STSG (~300 cm²).^6–8

Recell technology allows the preparation of a suspension to cover a wound of 1920 cm². This uses less donor skin and maximizes wound coverage with autograft. This is the first case study indicating the use of Recell in a patient with EDS. Limitations include cost, device availability, and the need for team familiarity, yet its biological benefits merit further study, particularly for patients with compromised healing. We invite further investigation into modalities of improved epithelialization in wounds in patients with unique healing challenges.^9,10

CONCLUSIONS

Wound healing is often made challenging with underlying comorbidities. The methods used in this case aim to guide surgeons on approaching wounds in patients with EDS, including the use of various classic and new skin grafting techniques for successful closure. This also helps avoid sequelae of complications of infection, expansion, or cosmetic and/or functional deformity with chronically open wounds. This case provided a novel surgical option to address these challenges and offers another modality to care for patients with EDS.^7,8

DISCLOSURE

The authors have no financial interest to declare in relation to the content of this article.

PATIENT CONSENT

Informed consent was obtained from all individual participants included in the study. Additional informed consent was obtained from all individual participants for whom identifying information is included in this article.

ETHICAL APPROVAL

This study was conducted in accordance with the ethical standards of Johns Hopkins University School of Medicine and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. It was exempt from approval by institutional review board of Johns Hopkins University School of Medicine. All subjects/participants provided their informed consent for inclusion before they participated in the study.